200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions.[57889] The primary endpoint of median progression-free survival (PFS), evaluated by independent central review, was significantly improved with pembrolizumab 2 mg/kg IV (n = 180) every 3 weeks (2.9 months) and pembrolizumab 10 mg/kg IV (n = 181) every 3 weeks (2.9 months) compared with investigator-choice chemotherapy (ICC) (n = 179; 2.7 months) in patients with unresectable stage III or IV melanoma who had disease progression following ipilimumab and had received prior treatment with a BRAF- and/or MEK-inhibitor (if BRAF V600 mutant-positive) in a second interim analysis of a multinational, randomized, phase 2 trial (the KEYNOTE-002 trial). ICC consisted of carboplatin/paclitaxel (n = 42) or single-agent carboplatin (n = 13), paclitaxel (n = 28), dacarbazine (n = 45), or temozolomide (n = 43). Ipilimumab-refractory melanoma was defined as progression within 24 weeks after at least 2 doses of ipilimumab. At a median follow-up time of 10 months, the 6-month PFS rates were 34% and 38% in the pembrolizumab 2 mg/kg and 10 mg/kg arms, respectively, compared with 16% in the ICC arm; additionally, the 9-month PFS rates were 24% and 29% compared with 8%, respectively. Treatment crossover to pembrolizumab occurred in 48% of patients who received ICC. Overall survival (OS) data are not yet mature.[59863]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions.[57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease recurrence or for up to 12 months in patients without disease recurrence. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions.[57889] The investigator-assessed median relapse-free survival (RFS; HR 0.62) and distant metastases-free survival (DMFS; HR 0.59) times were not reached in either arm after a median follow-up time of 39.4 months in patients with previously untreated, stage IIB or IIC melanoma after complete resection who received up to 1 year of adjuvant pembrolizumab or placebo in interim analyses of a randomized, placebo-controlled, phase 3 trial (KEYNOTE-716). The DMFS at 36 months was 84.4% with adjuvant pembrolizumab compared with 74.7% with placebo; the 36-month RFS rate was 76.2% versus 63.4%, respectively.[67512] [69434] In the 5-year analysis of another randomized, double-blind, phase 3 trial (EORTC 1325/KEYNOTE 054), up to 1 year of adjuvant therapy with pembrolizumab significantly improved the 5-year rate of RFS (55.4% vs. 38.3%) and DMFS (60.6% vs. 44.5%) compared with placebo in patients with resected high-risk stage III cutaneous melanoma. Of note, 70% of patients in the placebo arm with locoregional recurrence crossed over to an anti-PD-1/PD-L1-based treatment and 23% of patients in the pembrolizumab arm were rechallenged with pembrolizumab.[67178] [69435]

2 mg/kg (not to exceed 200 mg) IV repeated every 3 weeks until disease recurrence or for up to 12 months in patients without disease recurrence. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions.[57889] The investigator-assessed median relapse-free survival (RFS; HR 0.62) and distant metastases-free survival (DMFS; HR 0.59) times were not reached in either arm after a median follow-up time of 39.4 months in patients with previously untreated, stage IIB or IIC melanoma after complete resection who received up to 1 year of adjuvant pembrolizumab or placebo in interim analyses of a randomized, placebo-controlled, phase 3 trial (KEYNOTE-716). The DMFS at 36 months was 84.4% with adjuvant pembrolizumab compared with 74.7% with placebo; the 36-month RFS rate was 76.2% versus 63.4%, respectively. Pediatric patients aged 12 years and older were eligible for study enrollment; 2 pediatric patients were randomized (1 patient in the pembrolizumab arm and 1 patient in the placebo arm) in this trial.[67512] [69434] Efficacy for pediatric patients with stage III melanoma has been extrapolated from clinical trial data in adults with melanoma.[57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks for 12 weeks as neoadjuvant treatment or until disease progression that precludes definitive surgery or unacceptable toxicity, in combination with cisplatin (75 mg/m² IV on day 1) and pemetrexed (500 mg/m² IV on day 1) every 3 weeks for up to 4 cycles. Administer pembrolizumab prior to chemotherapy when given on the same day. Within 4 to 12 weeks after surgery, resume adjuvant pembrolizumab 200 mg IV every 3 weeks OR 400 mg IV every 6 weeks as monotherapy for 39 weeks or until disease recurrence or unacceptable toxicity. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. In a multicenter, randomized, double-blind clinical trial (KEYNOTE-671), perioperative treatment with pembrolizumab plus neoadjuvant platinum-based chemotherapy significantly improved the median overall survival (not reached vs. 52.4 months) and median event-free survival (not reached vs. 17 months) compared with perioperative placebo plus platinum-based chemotherapy in patients with previously untreated and resectable stage II, IIIA, or IIIB (N2) NSCLC. Platinum-based chemotherapy included cisplatin plus gemcitabine for patients with squamous histology and cisplatin plus pemetrexed for patients with nonsquamous histology.[69675] [57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks for 12 weeks as neoadjuvant treatment or until disease progression that precludes definitive surgery or unacceptable toxicity, in combination with cisplatin (75 mg/m² IV on day 1) and gemcitabine (1,000 mg/m² IV on days 1 and 8) every 3 weeks for up to 4 cycles. Administer pembrolizumab prior to chemotherapy when given on the same day. Within 4 to 12 weeks after surgery, resume adjuvant pembrolizumab 200 mg IV every 3 weeks OR 400 mg IV every 6 weeks as monotherapy for 39 weeks or until disease recurrence or unacceptable toxicity. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. In a multicenter, randomized, double-blind clinical trial (KEYNOTE-671), perioperative treatment with pembrolizumab plus neoadjuvant platinum-based chemotherapy significantly improved the median overall survival (not reached vs. 52.4 months) and median event-free survival (not reached vs. 17 months) compared with perioperative placebo plus platinum-based chemotherapy in patients with previously untreated and resectable stage II, IIIA, or IIIB (N2) NSCLC. Platinum-based chemotherapy included cisplatin plus gemcitabine for patients with squamous histology and cisplatin plus pemetrexed for patients with nonsquamous histology.[69675] [57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease recurrence, unacceptable toxicity, or for up to 12 months in patients without disease recurrence. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. In a multicenter, randomized, triple-blind, phase 3 clinical trial (KEYNOTE-091), adjuvant treatment with pembrolizumab after resection and 4 cycles of platinum-based chemotherapy significantly improved disease-free survival (DFS) compared with placebo in the subgroup of patients with stage 1B, II, or IIIA NSCLC which comprised 86% of the study population (58.7 months vs. 34.9 months); in the 14% of patients who did not receive adjuvant chemotherapy, the impact of adjuvant pembrolizumab on DFS was not statistically significant. Overall survival results were not mature.[57889] [68574]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. In a multicenter, open-label clinical trial (KEYNOTE-042; n = 1,274), treatment of PD-L1 positive (1% or more), EGFR and ALK-negative, stage III NSCLC in patients who were not candidates for surgical resection or definitive chemoradiation or metastatic NSCLC with pembrolizumab significantly improved median overall survival compared with investigator's choice of platinum-based chemotherapy (16.7 vs. 12.1 months); survival was higher in patients with TPS of 50% or more (20 months). Progression-free survival (PFS) was not significantly improved in patients with TPS of 1% or more (5.4 months vs. 6.5 months) or 50% or more (7.1 vs. 6.4 months). In patients with TPS 1% or more, the objective response rate was 27% in each arm; however, more prolonged responses were seen in patients who received pembrolizumab. A response of 12 months or longer was seen in 47% of responding patients treated with pembrolizumab compared with 16% of those who received chemotherapy; a response duration of 18 months or more was seen in 26% versus 6% of patients, respectively. Another clinical trial with a similar design to KEYNOTE-042 but only enrolling patients with TPS of 50% or more (KEYNOTE-024) was stopped early by an independent data and safety monitoring committee after demonstrating superiority of pembrolizumab compared with platinum-based chemotherapy with regard to PFS (10.3 vs. 6 months), despite a large percentage of patients (66%) in the chemotherapy arm crossing over to receive second-line therapy with pembrolizumab.[61268] [57889] After 5 years of follow-up, treatment with pembrolizumab significantly improved median overall survival (OS) in KEYNOTE-024 compared with platinum-based chemotherapy (26.3 months vs. 13.4 months); the estimated 5-year OS rate was 31.9% versus 16.3%, respectively.[66632]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression in combination with pemetrexed (500 mg/m² IV) on day 1 plus either carboplatin (AUC 5 IV) or cisplatin (75 mg/m² IV) on day 1 repeated every 21 days for 4 cycles. Administer pembrolizumab prior to pemetrexed and chemotherapy when given on the same day. Pembrolizumab therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Following completion of platinum-based therapy, pembrolizumab may be continued as maintenance therapy for up to 24 months, either alone or in combination with pemetrexed, until disease progression or unacceptable toxicity. In a multicenter double-blind clinical trial (KEYNOTE-189), patients with previously untreated metastatic, EGFR- and ALK-negative, nonsquamous NSCLC, regardless of PD-L1 status, were randomized to treatment with pemetrexed plus either cisplatin or carboplatin, in combination with either pembrolizumab (n = 410) or placebo (n = 206). After a median follow-up of 31 months, the median overall survival (22 months vs. 10.6 months), progression-free survival (9 months vs. 4.9 months), and overall response rate (48.3% vs. 19.9%) were significantly improved in the pembrolizumab arm. The median duration of response was 12.5 months for patients who received pembrolizumab plus pemetrexed/platinum chemotherapy compared with 7.1 months in those receiving placebo plus pemetrexed/platinum chemotherapy.[57889] [28376] [66703] [67147] [70417]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression in combination with carboplatin (AUC 6 IV on day 1) plus either paclitaxel (200 mg/m² IV on day 1) or nab-paclitaxel (100 mg/m² on days 1, 8, and 15) repeated every 3 weeks for 4 cycles. Administer pembrolizumab prior to chemotherapy when given on the same day. Pembrolizumab therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. In a multicenter, randomized, double-blind clinical trial (KEYNOTE-407), treatment with pembrolizumab plus carboplatin and either paclitaxel or nab-paclitaxel (n = 278) significantly improved median overall survival (17.1 months vs. 11.6 months) and progression-free survival (6.4 months vs. 4.8 months) compared with placebo plus carboplatin and paclitaxel/nab-paclitaxel (n = 281) in patients with metastatic squamous NSCLC. The objective response rate was also significantly improved in the pembrolizumab arm (58% vs. 35%), for a median duration of 7.2 months and 4.9 months, respectively.[57889] [66530]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions.[57889] In a multicenter, randomized, open-label clinical trial, treatment with pembrolizumab (n = 346) improved overall survival (OS) and progression-free survival (PFS) compared with docetaxel (n = 343) in patients with PD-L1-expressing (TPS, 1% or greater), platinum-resistant, metastatic NSCLC. In the subgroup of patients with TPS greater than or equal to 1%, OS in patients treated with pembrolizumab was 10.4 months compared with 8.5 months in those who received docetaxel and the objective response rate (ORR) was 18% versus 9%, respectively; PFS was not significantly different. Results were stronger in patients with TPS greater than or equal to 50%, with median OS of 14.9 months in the pembrolizumab arm versus 8.2 months in the docetaxel arm, and ORR 30% compared with 8%, respectively; the improvement in PFS was small but statistically significant in this subgroup (5.2 months vs. 4.1 months).[61369] [57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions.[57889] The overall response rate (ORR) was 58% (complete response (CR) rate, 30%) in 50 patients with advanced Merkel cell carcinoma who received pembrolizumab in a multicenter, phase 2 (KEYNOTE-017) trial. At a median follow-up of 31.8 (range, 0.4 to 56.9) months, the median progression-free survival time was 16.8 months and the median duration of response and overall survival time were not reached.[69693] In another multicenter, phase 2 (KEYNOTE-913) trial, the ORR was 49% (CR rate, 16%) in 55 patients with advanced Merkel cell carcinoma who received pembrolizumab. In these 2 trials, eligible patients (median age, 71 years; range, 46 to 91 years) were not amenable to definitive surgery or radiation therapy and had not previously received systemic therapy; 14% of patients had stage IIIB disease and 86% of patients had stage IV disease.[57889]

2 mg/kg (not to exceed 200 mg) IV repeated every 3 weeks until disease progression or up to 24 months in patients without progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. Efficacy for pediatric patients has been extrapolated from results from clinical trials in adult Merkel cell carcinoma patients.[57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression in combination with carboplatin (AUC 5 IV on day 1) and fluorouracil (1,000 mg/m² per day continuous IV infusion on days 1 to 4) repeated every 3 weeks for 6 cycles. Administer pembrolizumab prior to chemotherapy when given on the same day. Pembrolizumab therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue pembrolizumab for severe or life-threatening infusion-related reactions. Treatment with pembrolizumab plus fluorouracil and either carboplatin or cisplatin significantly improved median overall survival  (13 months vs. 10.7 months) compared with cetuximab plus fluorouracil and carboplatin/cisplatin in patients with previously untreated metastatic or unresectable, recurrent squamous cell head and neck cancer in a randomized, open-label trial (KEYNOTE-048); hazard ratios were similar in the intent-to-treat population (0.72), in patients with PD-L1 CPS of 1 or more (0.65), and in patients with CPS of 20 or more (0.6). Progression-free survival (PFS) was not significantly different between arms (4.9 months vs. 5.1 months). The objective response rate was 36% in each arm for a median duration of 6.7 months in the pembrolizumab arm and 4.3 months in the cetuximab arm; there were more complete responses in patients who received pembrolizumab (6% vs. 3%), respectively.[57889] [64769]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression in combination with cisplatin (100 mg/m² IV on day 1) and fluorouracil (1,000 mg/m² per day continuous IV infusion on days 1 to 4) repeated every 3 weeks for 6 cycles. Administer pembrolizumab prior to chemotherapy when given on the same day. Pembrolizumab therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue pembrolizumab for severe or life-threatening infusion-related reactions. Treatment with pembrolizumab plus fluorouracil and either carboplatin or cisplatin significantly improved median overall survival  (13 months vs. 10.7 months) compared with cetuximab plus fluorouracil and carboplatin/cisplatin in patients with previously untreated metastatic or unresectable, recurrent squamous cell head and neck cancer in a randomized, open-label trial (KEYNOTE-048); hazard ratios were similar in the intent-to-treat population (0.72), in patients with PD-L1 CPS of 1 or more (0.65), and in patients with CPS of 20 or more (0.6). Progression-free survival (PFS) was not significantly different between arms (4.9 months vs. 5.1 months). The objective response rate was 36% in each arm for a median duration of 6.7 months in the pembrolizumab arm and 4.3 months in the cetuximab arm; there were more complete responses in patients who received pembrolizumab (6% vs. 3%), respectively.[57889] [64769]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. Treatment with pembrolizumab monotherapy significantly improved median overall survival (12.3 months vs. 10.3 months) in patients with metastatic or unresectable, recurrent squamous cell head and neck cancer and CPS of 1 or more compared with cetuximab plus fluorouracil and carboplatin/cisplatin in a randomized, open-label clinical trial (KEYNOTE-048); in patients with CPS of 20 or more, median overall survival was 14.9 months versus 10.7 months, respectively. At the time of the interim and final analyses, there was no significant difference in OS for the overall population. Median progression-free survival (PFS) was not significantly different between treatment arms (3.2 months vs. 5 months). The objective response rate was 19% in patients who received pembrolizumab compared with 35% in the cetuximab arm, for a median duration of 20.9 months versus 4.5 months, respectively; complete responses occurred in 5% and 3% of patients, respectively.[57889] [64769]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. After a median follow-up of 8.9 months, treatment with pembrolizumab resulted in an objective response rate (ORR) of 16% (95% CI, 11% to 22%), with a complete response rate of 5% in a multicenter, non-randomized, open-label clinical trial of patients with platinum-resistant, recurrent or metastatic head and neck squamous cell carcinoma (n = 174). The median duration of response was not reached, but ranged from 2.4 months to more than 27.7 months; 23 of 28 responses lasted 6 months or longer. The ORR and duration of response were similar regardless of dosage regimen (10 mg/kg every 2 weeks or 200 mg every 3 weeks) or HPV status.[57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions.[57889] The median progression-free survival (PFS) time was significantly improved in patients with relapsed or refractory cHL who received pembrolizumab compared with brentuximab vedotin (13.2 months vs. 8.3 months; hazard ratio (HR) = 0.65; 95% CI, 0.48 to 0.88) in a multicenter, randomized, phase 3 (KEYNOTE-204) trial (n = 304). Patients (median age, 36 years) in this trial received a median of 2 prior therapies and were ineligible for (37%) or had relapsed after (63%) autologous hematopoietic stem-cell transplantation (ASCT).[69216] At a median follow-up of 63.7 months, the objective response rate (ORR) was 71.4% (complete response [CR] rate, 27.6%) in 210 patients with relapsed or refractory cHL who received pembrolizumab in a multicenter, multicohort, phase 2 (KEYNOTE-087) trial. The median duration of response (DOR) was 16.6 months, the median PFS time was 13.7 months, and the median overall survival time was not reached. Patients who achieved a CR and had received at least 6 months of pembrolizumab including 2 cycles beyond CR were allowed to discontinue therapy; these patients could receive a second course of pembrolizumab for up to 1 year if they subsequently experienced progressive disease. In 19 evaluable patients who received a second course of pembrolizumab, the ORR was 73.7% (CR, 36.8%) and the median DOR was 15.2 months. Patients (median age, 35 years; range, 18 to 76 years) in this trial had progressed after the most recent therapy or without a response their most recent ASCT and received a median of 4 (range, 1 to 12) prior systemic therapies; 83.3% had received prior brentuximab vedotin therapy.[69217]

2 mg/kg (not to exceed 200 mg) IV repeated every 3 weeks until disease progression or up to 24 months in patients without progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. Efficacy for pediatric patients has been extrapolated from results from clinical trials in adult cHL patients.[57889]

200 mg IV repeated every 3 weeks for up to 24 months was evaluated in a phase 2 trial (KEYNOTE-087 trial).[61092] Alternatively, pembrolizumab 400 mg IV every 6 weeks until disease progression or up to 24 months in patients without progression may be used. There does not appear to be any clinically significant differences in efficacy and safety between pembrolizumab dosages of 200 mg IV every 3 weeks or 400 mg IV every 6 weeks based on pharmacokinetic data and model-based simulations. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions.[57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without disease progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. In a multicenter, randomized clinical trial (KEYNOTE-045), treatment with pembrolizumab significantly improved median overall survival (10.3 vs. 7.4 months) and objective response rates (21% vs. 11%; complete response, 7% vs. 3%; partial response, 14% vs. 8%) for patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy treated with pembrolizumab (n = 270) compared with investigator's choice of chemotherapy (paclitaxel, n = 84; docetaxel, n = 84; vinflunine, n = 87); the median duration of response was not reached in the pembrolizumab arm, compared with 4.3 months in the chemotherapy arm. There was no significant difference in progression-free survival between treatment arms.[61782] [57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without disease progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. In a multicenter, randomized clinical trial (KEYNOTE-045), treatment with pembrolizumab significantly improved median overall survival (10.3 vs. 7.4 months) and objective response rates (21% vs. 11%; complete response, 7% vs. 3%; partial response, 14% vs. 8%) for patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy treated with pembrolizumab (n = 270) compared with investigator's choice of chemotherapy (paclitaxel, n = 84; docetaxel, n = 84; vinflunine, n = 87); the median duration of response was not reached in the pembrolizumab arm, compared with 4.3 months in the chemotherapy arm. There was no significant difference in progression-free survival between treatment arms. Fifteen percent of patients in this trial had disease progression following platinum-based neoadjuvant or adjuvant chemotherapy.[61782] [57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without disease progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. In a multicenter, open-label, single-arm clinical trial (n = 370; KEYNOTE-052), treatment with pembrolizumab resulted in an objective response rate of 29% (95% CI, 24% to 34%), with 10% complete responses and 20% partial responses, in patients with locally advanced or metastatic urothelial carcinoma who were not eligible for cisplatin-containing chemotherapy. The median duration of response was 30.1 months, with 67% of responses lasting 12 months and 52% lasting 24 months. The median overall survival was 11.3 months.[66073] [57889] In a multicenter, randomized trial, previously untreated patients with metastatic urothelial carcinoma who were eligible for platinum-containing chemotherapy (KEYNOTE-361) were randomized to treatment with pembrolizumab monotherapy, pembrolizumab with platinum-based chemotherapy to platinum-based chemotherapy alone. This study did not meet its major efficacy measures of improved progression-free survival or overall survival in the pembrolizumab plus chemotherapy arm. In an exploratory analysis, overall survival was similar in patients receiving pembrolizumab monotherapy versus chemotherapy in both the total population (15.6 months vs. 14.3 months) and in patients with CPS of 10% or higher (16.1 months vs. 15.2 months). The monotherapy arm of this trial was closed to accrual for patients with low PD-L1 expression (CPS less than 10%) upon the recommendation of the independent Data Monitoring Committee based on concerning survival data for PD-L1 inhibitor monotherapy in this trial and the IMvigor130 trial.[66963] [57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without disease progression, in combination with enfortumab vedotin (1.25 mg/kg [maximum, 125 mg] IV on days 1 and 8, every 21 days until disease progression or unacceptable toxicity). Administer pembrolizumab after completion of enfortumab vedotin when given on the same day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. In a multicenter, randomized, open-label clinical trial (KEYNOTE-A39), treatment with pembrolizumab plus enfortumab vedotin significantly improved overall survival (31.5 months vs. 16.1 months), progression-free survival (12.5 months vs. 6.3 months), and objective response rate (68% vs. 44%; complete response [CR], 29% vs. 12%) compared with platinum-based chemotherapy in patients with locally advanced or metastatic urothelial cancer with no prior systemic treatment for advanced disease. In an open-label, multicohort trial (KEYNOTE-869), treatment with pembrolizumab plus enfortumab vedotin resulted in a confirmed overall response rate of 68% (CR, 12%) in 3 cohorts of patients with previously untreated locally advanced or metastatic urothelial cancer who were ineligible for cisplatin-containing chemotherapy; the median duration of response was 22.1 months in 2 cohorts and was not reached in the third.[64845] [68834] [70064] [57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without disease progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. In pooled data from 5 multicenter, uncontrolled, open-label, multicohort, single-arm trials (KEYNOTE-016, KEYNOTE-164, KEYNOTE-028, KEYNOTE-012, and KEYNOTE-158), patients with MSI-H or dMMR solid tumors treated with pembrolizumab (10 mg/kg every 2 weeks or 200 mg every 3 weeks; n = 149) had an objective response rate of 39.6% (complete response, 7.4%; partial response, 32.2%) with a median duration of response not reached (range, 1.6+ to 22.7+ months); 78% of patients had a duration of response greater than or equal to 6 months.[57889]

2 mg/kg (not to exceed 200 mg) IV repeated every 3 weeks until disease progression or up to 24 months in patients without progression; the safety and efficacy of pembrolizumab in pediatric patients with MSI-H central nervous system cancers have not been established. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. Efficacy for pediatric patients has been extrapolated from results from clinical trials in adult MSI-H patients. In pooled data from 5 multicenter, uncontrolled, open-label, multicohort, single-arm trials (KEYNOTE-016, KEYNOTE-164, KEYNOTE-028, KEYNOTE-012, and KEYNOTE-158), adult patients with MSI-H or dMMR solid tumors treated with pembrolizumab (10 mg/kg every 2 weeks or 200 mg every 3 weeks; n = 149) had an objective response rate of 39.6% (complete response, 7.4%; partial response, 32.2%) with a median duration of response not reached (range, 1.6+ to 22.7+ months); 78% of patients had a duration of response greater than or equal to 6 months.[57889]

200 mg IV every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. In a randomized, controlled, phase 3 trial (the KEYNOTE-062 trial), first-line treatment of HER2-negative, PD-L1 positive, locally advanced/unresectable or metastatic gastric or GEJ cancer with pembrolizumab monotherapy was noninferior to cisplatin plus fluoropyrimidine chemotherapy for overall survival; the effect on overall survival was greater in patients with PD-L1 CPS of 10 or higher although due to protocol design, this outcome was not statistically analyzed. Patients receiving pembrolizumab monotherapy also experienced fewer treatment-related adverse reactions.[65919]

200 mg IV every 3 weeks OR 400 mg IV every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months in patients without disease progression. Administer in combination with trastuzumab (8 mg/kg IV on day 1 of cycle 1, followed 3 weeks later by 6 mg/kg IV every 3 weeks in subsequent cycles) followed by fluoropyrimidine- and platinum-containing chemotherapy. Administer pembrolizumab prior to trastuzumab and chemotherapy when given on the same day. Treatment with pembrolizumab plus trastuzumab and investigator's choice of chemotherapy (cisplatin plus fluorouracil, or capecitabine plus oxaliplatin) significantly improved objective response rate (ORR) (74% vs. 52%; complete response, 11% vs. 3.1%) compared with placebo plus trastuzumab and chemotherapy in the overall population of patients with previously untreated HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma at an interim analysis of a multicenter, randomized phase 3 trial (KEYNOTE-811); in the clinical trial, treatment with fluorouracil could continue after completion of 6 cycles of cisplatin, per protocol. In a prespecified subgroup analysis, the ORR in patients with PD-L1 positive disease was 76% in the pembrolizumab arm versus 51% in the control arm; in patients who were PD-L1 negative, the ORR was 63% versus 58%, respectively. In a subsequent interim analysis, the hazard ratios for progression-free survival and overall survival were nonsignificant in patients with PD-L1 negative disease.[69837] [57889] [66655]

200 mg IV every 3 weeks OR 400 mg IV every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months in patients without disease progression. Administer in combination with fluoropyrimidine- and platinum-containing chemotherapy; administer pembrolizumab prior to chemotherapy when given on the same day. Treatment with pembrolizumab plus investigator's choice of chemotherapy (cisplatin and 5FU [FP] or oxaliplatin and capecitabine [CapeOx]) significantly improved overall survival (12.9 months vs. 11.5 months), progression-free survival (6.9 months vs. 5.6 months), and objective response rate (51% vs. 42%; complete response, 9% vs. 6%) compared with placebo plus chemotherapy in patients with HER2-negative advanced gastric or GEJ cancer who had not previously received systemic therapy for metastatic disease in a planned interim analysis of a multicenter, randomized, double-blind, phase 3 clinical trial (KEYNOTE-859); 86% of patients received CapeOx. The median duration of response was 8 months versus 5.7 months, respectively. Seventy-eight percent of patients had PD-L1 positive tumors with a CPS greater than or equal to 1. Differences in response were more pronounced in the subgroups of patients with tumors that had PD-L1 CPS greater than or equal to 1, and in those with PD-L1 CPS greater than or equal to 10.[57889] [69908]

Dosage not available.

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions.[57889] In a nonrandomized, phase 2 (KEYNOTE-170) trial, the primary endpoint of objective response rate (assessed by blinded central review) was 45% (complete response (CR) rate, 13%) following pembrolizumab therapy in 53 patients with PMBCL who had relapsed or refractory disease after at least 2 prior lines of therapy. At a median follow-up time of 48.7 (range, 41.2 to 56.2) months, the investigator-assessed best overall response rate was 41.5% (CR rate, 20.8%) in patients who received pembrolizumab in the KEYNOTE-170 trial. The median progression-free survival (PFS) and overall survival (OS) times were 4.3 months and 22.3 months, respectively. In this study, patients (median age, 33 years; range, 20 to 61 years) had received a median of 3 (range, 2 to 8) prior therapies including rituximab; 26% of patients had previously received an autologous stem-cell transplant and 32% of patients had received prior radiation therapy.[70186] [70187] At a median follow-up time of 29.1 months, the objective response rate was 48% (CR rate, 33%) in a cohort of patients with PMBCL who experienced relapse after or were ineligible for autologous stem-cell transplantation (n = 21) in a phase 1b (KEYNOTE-013) trial. After an additional 26 months of follow-up, the median PFS and OS times were 19 months and 37.1 months, respectively.[70186] [70189]

2 mg/kg (not to exceed 200 mg) IV repeated every 3 weeks until disease progression or up to 24 months in patients without progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. Efficacy for pediatric patients has been extrapolated from results from clinical trials in adult PMBCL patients.[57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. The overall response rate was 14.3% in a cohort of 77 patients with recurrent or metastatic PD-L1-expressing cervical cancer who received pembrolizumab in a multi-cohort, nonrandomized trial (KEYNOTE-158). Additionally, a complete response was achieved in 2.6% of patients. At a median follow-up time of 11.7 months, the median duration of response was not reached (range, 4.1 to 18.6+ months); 91% of patients had a response duration lasting 6 months or longer. Patients (median age, 45 years; range, 27 to 75 years) in this study had received 1 (35%) or 2 (65%) lines of prior therapy.[57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression. Use in combination with paclitaxel 175 mg/m² IV on day 1 plus either cisplatin 50 mg/m² IV on day 1 or 2 OR carboplatin AUC of 5 IV on day 1, with or without bevacizumab 15 mg/kg IV on day 1 every 3 weeks. Administer pembrolizumab prior to chemotherapy when given on the same day. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions.[57889] At the first interim analysis of a multicenter, randomized, double-blind, phase 3 trial (KEYNOTE-826), treatment with pembrolizumab plus chemotherapy significantly improved the median progression-free survival compared with placebo plus chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer (10.4 months vs. 8.2 months); bevacizumab was added to treatment in 63% of patients in this trial. The objective response rate was 68% in the pembrolizumab arm compared with 50% in the placebo arm, respectively (complete response, 23% vs. 14%); the median duration of response was 18 months versus 10.4 months, respectively. In the final overall survival (OS) analysis, treatment with pembrolizumab plus chemotherapy significantly improved the median OS compared with placebo plus chemotherapy in the intent-to-treat population (26.4 months vs. 16.8 months), the PD-L1 CPS of greater than or equal to 1 population (28.6 months vs. 16.5 months), and in the PD-L1 CPS greater than or equal to 10 population (29.6 months vs. 17.4 months).[67047] [69855]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months in patients without progression. Administer in combination with cisplatin (40 mg/m² IV once weekly for 5 cycles) and radiotherapy (external beam radiation therapy [ERBT] followed by brachytherapy [BT]). Administer pembrolizumab prior to chemoradiotherapy when given on the same day. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. Treatment with pembrolizumab plus cisplatin and ERBT followed by BT (chemoradiotherapy [CRT]) was compared with placebo plus CRT in a multicenter, randomized, double-blind clinical trial (KEYNOTE-A18) which included patients with cervical cancer who had not previously received any definitive surgery, radiation, or systemic therapy for cervical cancer; of these patients (n = 1,060), 56% had FIGO 2014 stage III to IVA disease and 44% had FIGO 2014 stage 1B2 to IIB node positive disease. In the subset of patients with FIGO 2014 stage III to IVA disease, the addition of pembrolizumab to CRT significantly improved the median progression-free survival PFS by investigator, which was not reached in both arms with a lower level of the 95% confidence interval not reached in the pembrolizumab arm compared with 18.8 months in the placebo arm; the 12-month rate of PFS was 81% versus 70%, respectively. Overall survival results were not mature at the time of the PFS analysis.[57889] [70191]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without disease progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. Treatment with pembrolizumab significantly improved median overall survival (13.9 months vs. 13 months) compared with placebo in patients with previously-treated Barcelona Clinical Liver Cancer (BCLC) Stage B or C hepatocellular cancer in a multicenter, randomized clinical trial conducted in Asia; 79% of patients had active hepatitis B. The median progression-free survival was 2 months in the pembrolizumab arm compared with 2.3 months in the placebo arm; the objective response rate was 11% versus 1.6%, respectively, with a median duration of 23.9 months in patients who received pembrolizumab and 5.6 months in those who received placebo. Complete responses were achieved by 0.9% of patients in the pembrolizumab arm and 0.8% of those in the placebo arm.[70283] [57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease recurrence, unacceptable toxicity, or for up to 12 months in patients without disease recurrence. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. Adjuvant treatment with pembrolizumab significantly improved disease-free survival (DFS) compared with placebo in patients with renal cell cancer with an intermediate-high or high risk of recurrence after nephrectomy or M1 with no evidence of disease after nephrectomy in a randomized clinical trial (KEYNOTE-564); the 24-month DFS rate was 77% versus 68%, respectively.[57889] [67129]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression in combination with axitinib (initial dose, 5 mg PO twice daily). The axitinib dosage may be increased to 7 mg twice daily and then to 10 mg twice daily at intervals of 6 weeks or longer in normotensive patients (BP less than or equal to 150/90) who tolerate the lower dosage for at least 2 consecutive weeks with no greater than grade 2 adverse reactions. Continue axitinib until disease progression or unacceptable toxicity.[63966] [57889] Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.[48494] Pembrolizumab therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions; permanently discontinue therapy for severe or life-threatening infusion-related reactions.[57889] Combination therapy with pembrolizumab and axitinib significantly improved median overall survival (45.7 months vs. 40.1 months) and median progression-free survival (15.7 months vs. 11.1 months) compared with sunitinib in patients with advanced renal cell cancer in the final analysis of an open-label, phase 3 clinical trial (KEYNOTE-426). The objective response rate was 60.4% (complete response [CR], 10%) versus 39.6% (CR, 3.5%), respectively; the median duration of response was 23.6 months in patients receiving combination therapy compared with 15.3 months for patients treated with sunitinib.[67485] [63966] [57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks in combination with lenvatinib (20 mg orally once daily), continue treatment until disease progression or for up to 24 months in patients without progression. After 2 year of combination therapy, lenvatinib may be continued as a single agent until disease progression or unacceptable toxicity. Pembrolizumab therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions; permanently discontinue therapy for severe or life-threatening infusion-related reactions.[57889] [58782] Investigator-assessed median progression-free survival was significantly improved with lenvatinib plus pembrolizumab compared with sunitinib (23.9 months vs. 9.2 months) in patients with previously untreated advanced RCC with a clear-cell component in a 3-arm, randomized (1:1:1), phase 3 trial (CLEAR/KEYNOTE-581); the objective response rate (ORR) was 71% versus 36%, respectively (complete response, 16% vs. 4%).[66893] In an updated overall survival [OS] analysis, the median OS for patients treated with pembrolizumab plus lenvatinib was 53.7 months compared with 54.3 months for those who received sunitinib.[69686] First-line treatment with pembrolizumab plus lenvatinib also resulted in an ORR of 51% (CR, 8%) for a median duration of 19.5 months in a multicenter, single-arm trial of patients with advanced or metastatic non-clear cell RCC (KEYNOTE-B61).[70731]

Dosage not established.

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. Treatment with pembrolizumab significantly improved the median overall survival (OS) (9.3 months vs. 6.7 months) and progression-free survival (3.2 months vs. 2.3 months) compared with investigators' choice of chemotherapy (i.e., paclitaxel, docetaxel, or irinotecan monotherapy) in patients with recurrent, progressive, PD-L1 positive (CPS 10 or higher), locally advanced or metastatic esophageal or GEJ cancer in a randomized clinical trial (KEYNOTE-181); the estimated 12-month survival was 43% versus 20%, respectively; median OS was 8.2 versus 7.1 months, respectively, in patients with squamous cell carcinoma, and was unchanged (7.1 months) in all patients. The objective response rate was 21.5% in the pembrolizumab arm compared with 6.1% in the chemotherapy arm (complete response, 3.7% vs. 0.9%); the median duration of response was 9.3 months versus 7.7 months, respectively.[57889] [66536]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression. Administer pembrolizumab prior to chemotherapy when given on the same day. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. Administer in combination with cisplatin (80 mg/m² IV on day 1 every 3 weeks for up to 6 cycles) and fluorouracil (800 mg/m² IV per day continuously on days 1 to 5, every 3 weeks for up to 24 months). In a randomized clinical trial (KEYNOTE-590), treatment with pembrolizumab plus cisplatin and fluorouracil significantly improved median overall survival (12.4 months vs. 9.8 months) and median progression-free survival (6.3 months vs. 5.8 months) compared with placebo plus cisplatin and fluorouracil in patients with locally advanced or metastatic esophageal/GEJ tumors who were not candidates for surgical resection or definitive chemoradiation. In a prespecified formal test in patients with PD-L1 CPS of 10 or higher, the median overall survival was 13.5 months in pembrolizumab-treated patients compared with 9.4 months for those who received placebo; in an exploratory analysis, the median overall survival was 10.5 months versus 10.6 months, respectively, for patients with PD-L1 CPS less than 10. The overall response rate was also significantly improved in intent-to-treat patients who received pembrolizumab (45% for a median duration of 8.3 months; complete response [CR], 6%) compared with placebo (29% for a median duration of 6 months; CR, 2.4%).[57889] [66945]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or for up to 24 months in patients without disease progression in combination with lenvatinib 20 mg PO once daily until disease progression. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Treatment with pembrolizumab plus lenvatinib significantly improved the median progression-free survival (6.6 months vs. 3.8 months) and overall survival (17.4 months vs. 12 months) compared with doxorubicin or paclitaxel in patients with advanced endometrial cancer who had been previously treated with at least one prior platinum-based chemotherapy regimen in any setting and were not MSI-H or dMMR in a multicenter, randomized, open-label clinical trial (KEYNOTE-775). The objective response rate was also significantly improved in the pembrolizumab/lenvatinib arm (30% vs. 15%; complete response, 5% vs. 3%) for a median duration of 9.2 months versus 5.7 months, respectively.[57889] [58782] [67484]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression. In 2 cohorts of a multicenter, open-label, noncomparative, multicohort, phase 2 trial (KEYNOTE-158), the objective response rate was 46% (complete response, 12%) for a median duration that was not reached in patients with unresectable or metastatic MSI-H or dMMR endometrial cancer received at least 1 dose of pembrolizumab; of patients who responded, 68% had a response duration of at least 12 months and 44% had a response duration of at least 24 months.[57889] [67483]

200 mg IV every 3 weeks OR 400 mg IV every 6 weeks until disease progression or for up to 24 months in patients without disease progression in combination with carboplatin AUC 5 IV and paclitaxel 175 mg/m² IV on day 1 every 3 weeks for 6 cycles. Administer pembrolizumab prior to chemotherapy when given on the same day. Treatment with pembrolizumab plus carboplatin and paclitaxel significantly improved progression-free survival (PFS) in patients with advanced or recurrent endometrial cancer compared with placebo plus carboplatin and paclitaxel in a multicenter, randomized, double-blind clinical trial (KEYNOTE-868) in both the mismatch repair deficient (dMMR) (not reached vs. 6.5 months) and mismatch repair proficient (pMMR) (11.1 months vs. 8.5 months) cohorts.[57889] [70798]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until persistent or recurrent high-risk NMIBC, disease progression, or for up to 24 months in patients without disease progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. Treatment of BCG-unresponsive, high-risk NMIBC with pembrolizumab resulted in a complete response rate of 41% for a median duration of 16.2 months in a multicenter, noncomparative trial (n = 96).[57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression, unacceptable toxicity, or for up to 24 months in patients without progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. Pembrolizumab was administered to 10 cohorts of patients with various previously-treated unresectable or metastatic solid tumors with TMB-H in a prospectively-planned, retrospective analysis of a multicenter, noncomparative trial (KEYNOTE-158). For patients with at least 13 mut/Mb, the objective response rate was 37% (complete response [CR], 3%) for a median duration that was not reached; 58% of patients had a duration of response of at least 12 months, and 50% had a duration of at least 24 months. For patients with at least 10 mut/Mb, the objective response rate was 29% (complete response [CR], 4%) for a median duration that was not reached; 57% of patients had a duration of response of at least 12 months, and 50% had a duration of at least 24 months. The highest response rates were seen in patients with endometrial cancer (n = 15; 47%), neuroendocrine cancer (n = 5; 40%), cervical cancer (n = 16; 31%), and small cell lung cancer (n = 34; 29%); two patients with thyroid cancer were treated and both achieved complete response for a duration of 8.2 months and more than 33.2 months at last follow-up.[57889]

2 mg/kg (not to exceed 200 mg) IV repeated every 3 weeks until disease progression, unacceptable toxicity, or for up to 24 months in patients without progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. The use of pembrolizumab in pediatric patients is supported by evidence from adequate and well-controlled studies of pembrolizumab in adults with additional pharmacokinetic and safety data in pediatric patients. Pembrolizumab was administered to 10 cohorts of patients with various previously-treated unresectable or metastatic solid tumors with TMB-H in a prospectively-planned, retrospective analysis of a multicenter, noncomparative trial (KEYNOTE-158). For patients with at least 13 mut/Mb, the objective response rate was 37% (complete response [CR], 3%) for a median duration that was not reached; 58% of patients had a duration of response of at least 12 months, and 50% had a duration of at least 24 months. For patients with at least 10 mut/Mb, the objective response rate was 29% (complete response [CR], 4%) for a median duration that was not reached; 57% of patients had a duration of response of at least 12 months, and 50% had a duration of at least 24 months. The highest response rates were seen in patients with endometrial cancer (n = 15; 47%), neuroendocrine cancer (n = 5; 40%), cervical cancer (n = 16; 31%), and small cell lung cancer (n = 34; 29%); two patients with thyroid cancer were treated and both achieved complete response for a duration of 8.2 months and more than 33.2 months at last follow-up.[57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression. Pembrolizumab therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions; permanently discontinue therapy for severe or life-threatening infusion-related reactions. In a nonrandomized, phase 2 (KEYNOTE-629) trial, treatment with pembrolizumab resulted in objective response rates of 35% (complete response (CR), 11%) and 50% (CR, 17%) in patients with recurrent or metastatic cSCC (n = 105; 1 or more prior lines of therapy, 87%) or locally advanced cSCC (n = 54; 1 or more prior lines of therapy, 22%), respectively. In patients with recurrent or metastatic cSCC, the median duration of response was not reached (range, 2.7 months to more than 30.4 months) at a median follow-up time of 23.8 months; the duration of response was at least 12 months in 68% of patients. In patients with locally advanced cSCC, the median duration of response was not reached (range, 1 month to more than 17.2 months) at a median follow-up time of 13.4 months; the duration of response was at least 12 months in 37% of patients.[57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without disease progression. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions; permanently discontinue therapy for severe or life-threatening infusion-related reactions. At a median follow-up time of 27.6 months (range, 0.2 to 48.3 months), the median progression-free survival time was significantly improved in patients with previously untreated unresectable or metastatic MSI-H or dMMR colorectal cancer who received pembrolizumab compared with standard chemotherapy (16.5 months vs. 8.2 months) in a randomized, phase 3 trial (KEYNOTE-177). The overall survival data were not mature at the time of this analysis. In this trial, patients in the standard chemotherapy arm received therapy every 2 weeks that consisted of either mFOLFOX6 (oxaliplatin 85 mg/m² IV on day 1; leucovorin 400 mg/m² (or levoleucovorin 200 mg/m²) IV on day 1; and fluorouracil 400 mg/m² IV bolus on day 1, then fluorouracil 2,400 mg/m² IV over 46 to 48 hours) or FOLFIRI (irinotecan 180 mg/m² IV on day 1; leucovorin 400 mg/m² (or levoleucovorin 200 mg/m²) IV on day 1; and fluorouracil 400 mg/m² IV bolus on day 1, then fluorouracil 2,400 mg/m² IV over 46 to 48 hours). Bevacizumab (5 mg/kg IV on day 1) or cetuximab (400 mg/m² IV on first infusion, then 250 mg/m² once weekly) were added to mFOLFOX6 or FOLFIRI in some patients. In pooled data from 4 multicenter, uncontrolled, open-label, multicohort, single-arm trials (KEYNOTE-016, KEYNOTE-164, KEYNOTE-028, and KEYNOTE-158), the objective response rate was 36% in 90 patients with MSI-H or dMMR colorectal cancer who received pembrolizumab (10 mg/kg every 2 weeks or 200 mg every 3 weeks). The median duration of response ranged from 1.6+ to 22.7+ months in these patients. Most (84%) patients with colorectal cancer had received 2 or more prior lines of therapy.[57889]

200 mg IV repeated every 3 weeks for 8 doses OR 400 mg IV repeated every 6 weeks for 4 doses (up to 24 weeks or until disease progression or unacceptable toxicity). Administer pembrolizumab in combination with paclitaxel (80 mg/m² IV once weekly) plus carboplatin (AUC 5 IV on day 1 every 3 weeks) for 4 cycles (12 weeks); alternatively, carboplatin may be dosed once weekly at an AUC of 1.5 IV for 12 weeks. After completion of 4 cycles of paclitaxel and carboplatin, continue neoadjuvant pembrolizumab in combination with doxorubicin (60 mg/m² IV) plus cyclophosphamide (600 mg/m² IV) on day 1 every 3 weeks for 4 cycles, followed by surgery. Administer pembrolizumab prior to chemotherapy when given on the same day. After surgery, administer pembrolizumab 200 mg IV every 3 weeks for up to 9 doses OR 400 mg IV repeated every 6 weeks for up to 5 doses or until disease progression or unacceptable toxicity. Do not administer adjuvant pembrolizumab monotherapy to patients with disease progression or unacceptable toxicity related to neoadjuvant treatment with pembrolizumab plus chemotherapy. Pembrolizumab may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions; permanently discontinue therapy for severe or life-threatening infusion-related reactions. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Patients with high-risk (tumor size more than 1 cm but up to and including 2 cm in diameter with nodal involvement; or tumor size more than 2 cm in diameter regardless of nodal involvement), early stage triple-negative breast cancer were randomized to neoadjuvant treatment with pembrolizumab or placebo in combination with carboplatin and paclitaxel, followed by anthracycline and cyclophosphamide in a phase 3 clinical trial (KEYNOTE-522); after definitive surgery, patients received adjuvant pembrolizumab or placebo. Treatment with pembrolizumab plus chemotherapy significantly improved the rate of pathologic complete response (pCR) (63% vs. 55.6%) compared with placebo plus chemotherapy. The median event-free survival (EFS) was not reached in either arm, although EFS at 18 months was 91.3% in patients who received pembrolizumab compared with 85.3% in those who received placebo (HR 0.63; 95% CI, 0.43 to 0.93); overall survival results are immature.[66036] [57889]

200 mg IV repeated every 3 weeks for 8 doses OR 400 mg IV repeated every 6 weeks for 4 doses (up to 24 weeks or until disease progression or unacceptable toxicity). Administer pembrolizumab in combination with paclitaxel (80 mg/m² IV once weekly) plus carboplatin (AUC 5 IV on day 1 every 3 weeks) for 4 cycles (12 weeks); alternatively, carboplatin may be dosed once weekly at an AUC of 1.5 IV for 12 weeks. After completion of 4 cycles of paclitaxel and carboplatin, continue neoadjuvant pembrolizumab in combination with epirubicin (90 mg/m² IV) plus cyclophosphamide (600 mg/m² IV) on day 1 every 3 weeks for 4 cycles, followed by surgery. Administer pembrolizumab prior to chemotherapy when given on the same day. After surgery, administer pembrolizumab 200 mg IV every 3 weeks for up to 9 doses OR 400 mg IV repeated every 6 weeks for up to 5 doses or until disease progression or unacceptable toxicity. Do not administer adjuvant pembrolizumab monotherapy to patients with disease progression or unacceptable toxicity related to neoadjuvant treatment with pembrolizumab plus chemotherapy. Pembrolizumab may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions; permanently discontinue therapy for severe or life-threatening infusion-related reactions. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Neoadjuvant treatment with pembrolizumab in combination with carboplatin and paclitaxel, followed by neoadjuvant pembrolizumab plus anthracycline and cyclophosphamide significantly improved the rate of pathologic complete response (pCR) (63% vs. 55.6%) compared with placebo plus chemotherapy in patients with high-risk TNBC (tumor size more than 1 cm but up to and including 2 cm in diameter with nodal involvement; or tumor size more than 2 cm in diameter regardless of nodal involvement) in a phase 3 trial (KEYNOTE-522). The median event-free survival (EFS) was not reached in either arm, although EFS at 18 months was 91.3% in patients who received pembrolizumab compared with 85.3% in those who received placebo (HR 0.63; 95% CI, 0.43 to 0.93); overall survival results are immature.[66036] [57889]

200 mg IV every 3 weeks until disease progression or unacceptable toxicity for up to 9 doses; OR 400 mg IV repeated every 6 weeks until disease progression or unacceptable toxicity for up to 5 doses. Pembrolizumab may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions; permanently discontinue therapy for severe or life-threatening infusion-related reactions. Patients with high-risk (tumor size more than 1 cm but up to and including 2 cm in diameter with nodal involvement; or tumor size more than 2 cm in diameter regardless of nodal involvement), early stage triple-negative breast cancer were randomized to neoadjuvant treatment with pembrolizumab or placebo in combination with carboplatin and paclitaxel, followed by anthracycline and cyclophosphamide in a phase 3 clinical trial (KEYNOTE-522); after definitive surgery, patients received adjuvant pembrolizumab or placebo. Treatment with pembrolizumab plus chemotherapy significantly improved the rate of pathologic complete response (pCR) (63% vs. 55.6%) compared with placebo plus chemotherapy. The median event-free survival (EFS) was not reached in either arm, although EFS at 18 months was 91.3% in patients who received pembrolizumab compared with 85.3% in those who received placebo (HR 0.63; 95% CI, 0.43 to 0.93); overall survival results are immature.[66036] [57889]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression in combination with nab-paclitaxel (100 mg/m² on days 1, 8, and 15, every 28 days); the number of cycles of nab-paclitaxel was not specified.[66122] [66123] [57889] Administer pembrolizumab prior to chemotherapy when given on the same day. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. In a multicenter, double-blind clinical trial (KEYNOTE-355), patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the metastatic setting were randomized to treatment with either pembrolizumab or placebo in combination with paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin regardless of tumor PD-L1 expression. The addition of pembrolizumab to chemotherapy significantly improved the median progression-free survival (9.7 months vs. 5.6 months) compared with placebo plus chemotherapy in the subgroup of patients with a CPS of 10 or more in a prespecified interim analysis. At the prespecified final analysis, the median overall survival was also significantly improved in the pembrolizumab arm (23 months versus 16.1 months, respectively). The objective response rate was 53% compared with 40%, respectively (complete response, 17% vs. 13%) for a median duration of 19.3 months in the pembrolizumab arm and 7.3 months in the placebo arm.[57889] [66123]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression in combination with paclitaxel (90 mg/m² on days 1, 8, and 15, every 28 days); the number of cycles of paclitaxel was not specified.[66122] [66123] [57889] Administer pembrolizumab prior to chemotherapy when given on the same day. To prevent hypersensitivity reactions, all patients should be premedicated with dexamethasone 20 mg PO approximately 12 and 6 hours before paclitaxel, diphenhydramine 50 mg IV (or equivalent) 30 to 60 minutes before paclitaxel, and an IV H2-blocker 30 to 60 minutes before paclitaxel.[29200] Pembrolizumab therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. In a multicenter, double-blind clinical trial (KEYNOTE-355), patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the metastatic setting were randomized to treatment with either pembrolizumab or placebo in combination with paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin regardless of tumor PD-L1 expression. The addition of pembrolizumab to chemotherapy significantly improved the median progression-free survival (9.7 months vs. 5.6 months) compared with placebo plus chemotherapy in the subgroup of patients with a CPS of 10 or more in a prespecified interim analysis. At the prespecified final analysis, the median overall survival was also significantly improved in the pembrolizumab arm (23 months versus 16.1 months, respectively). The objective response rate was 53% compared with 40%, respectively (complete response, 17% vs. 13%) for a median duration of 19.3 months in the pembrolizumab arm and 7.3 months in the placebo arm.[57889] [66123]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression in combination with gemcitabine (1,000 mg/m² IV on days 1 and 8, every 21 days) and carboplatin (AUC 2 IV on days 1 and 8, every 21 days); the number of cycles of gemcitabine plus carboplatin was not specified.[66122] [66123] [57889] Administer pembrolizumab prior to chemotherapy when given on the same day. Pembrolizumab therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. In a multicenter, double-blind clinical trial (KEYNOTE-355), patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the metastatic setting were randomized to treatment with either pembrolizumab or placebo in combination with paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin regardless of tumor PD-L1 expression. The addition of pembrolizumab to chemotherapy significantly improved the median progression-free survival (9.7 months vs. 5.6 months) compared with placebo plus chemotherapy in the subgroup of patients with a CPS of 10 or more in a prespecified interim analysis. At the prespecified final analysis, the median overall survival was also significantly improved in the pembrolizumab arm (23 months versus 16.1 months, respectively). The objective response rate was 53% compared with 40%, respectively (complete response, 17% vs. 13%) for a median duration of 19.3 months in the pembrolizumab arm and 7.3 months in the placebo arm.[57889] [66123]

200 mg IV repeated every 3 weeks OR 400 mg IV repeated every 6 weeks until disease progression or up to 24 months in patients without progression. Administer in combination with cisplatin (25 mg/m² IV) plus gemcitabine (1,000 mg/m² IV) on days 1 and 8, every 3 weeks; in KEYNOTE-966, treatment with cisplatin was limited to 8 cycles and there was no limit to the number of cycles of gemcitabine. Administer pembrolizumab prior to chemotherapy when given on the same day. Therapy may need to be temporarily withheld or permanently discontinued in patients who develop immune-related reactions. Permanently discontinue therapy for severe or life-threatening infusion-related reactions. In a multicenter, randomized, double-blind phase 3 clinical trial (KEYNOTE-966), treatment with pembrolizumab in combination with cisplatin and gemcitabine significantly improved the median overall survival compared with placebo plus cisplatin and gemcitabine (12.7 months vs. 10.9 months) in patients with locally advanced unresectable or metastatic biliary tract cancer who had not received prior systemic therapy in the advanced disease setting. The median progression-free survival was 6.5 months in the pembrolizumab arm compared with 5.6 months in the placebo arm, and the median objective response rate was 29% in each arm (complete response, 2.1% vs. 1.3%); the median duration of response was 8.3 months vs. 6.8 months, respectively.[57889] [69750]