Pembrolizumab alone

A phase III open-label study (KEYNOTE-024) randomly assigned 305 patients with previously untreated, advanced NSCLC with PD-L1 expression on 50% or more tumor cells and no sensitizing EGFR variants or ALK translocations to either intravenous pembrolizumab (200 mg every 3 weeks for up to 35 cycles) or platinum-based chemotherapy (four to six cycles, investigator’s choice; pemetrexed maintenance was allowed for nonsquamous tumors).[89] The primary end point was PFS.

A phase III open-label study (KEYNOTE-024) randomly assigned 305 patients with previously untreated, advanced NSCLC with PD-L1 expression on 50% or more tumor cells and no sensitizing EGFR variants or ALK translocations to either intravenous pembrolizumab (200 mg every 3 weeks for up to 35 cycles) or platinum-based chemotherapy (four to six cycles, investigator’s choice; pemetrexed maintenance was allowed for nonsquamous tumors).[89] The primary end point was PFS.

PD-L1 expression was centrally assessed using the PD-L1 immunohistochemistry 22C3 pharmDx assay. PD-L1 tumor expression of 50% or more was found in 30.2% of 1,653 patient samples that were examined.

A phase III open-label study (KEYNOTE-024) randomly assigned 305 patients with previously untreated, advanced NSCLC with PD-L1 expression on 50% or more tumor cells and no sensitizing EGFR variants or ALK translocations to either intravenous pembrolizumab (200 mg every 3 weeks for up to 35 cycles) or platinum-based chemotherapy (four to six cycles, investigator’s choice; pemetrexed maintenance was allowed for nonsquamous tumors).[89] The primary end point was PFS.

Pembrolizumab demonstrated significant improvement in median PFS (10.3 months vs. 6.0 months; HR, 0.50; 95% CI, 0.37–0.68; P < .001). The overall response rate (44.8% vs. 27.8%), the median DOR (NR, [range, 1.9–14.5 months] vs. 6.3 months [range, 2.1–12.6 months]), and the estimated rate of OS at 6 months (80.2% vs. 72.4%; HR, 0.60; 95% CI, 0.41–0.89; P = .005) were all higher with pembrolizumab than with chemotherapy.

A phase III open-label study (KEYNOTE-024) randomly assigned 305 patients with previously untreated, advanced NSCLC with PD-L1 expression on 50% or more tumor cells and no sensitizing EGFR variants or ALK translocations to either intravenous pembrolizumab (200 mg every 3 weeks for up to 35 cycles) or platinum-based chemotherapy (four to six cycles, investigator’s choice; pemetrexed maintenance was allowed for nonsquamous tumors).[89] The primary end point was PFS.

Further follow-up of this study confirmed an OS advantage in favor of pembrolizumab; the median OS for patients who received pembrolizumab was 30 months (95% CI, 18.3 months–NR) versus 14.2 months for patients who received chemotherapy, with a 75% crossover to immunotherapy afterwards, suggesting the crossover did not impact survival.[92]

A phase III open-label study (KEYNOTE-024) randomly assigned 305 patients with previously untreated, advanced NSCLC with PD-L1 expression on 50% or more tumor cells and no sensitizing EGFR variants or ALK translocations to either intravenous pembrolizumab (200 mg every 3 weeks for up to 35 cycles) or platinum-based chemotherapy (four to six cycles, investigator’s choice; pemetrexed maintenance was allowed for nonsquamous tumors).[89] The primary end point was PFS.

Adverse events (any grade) were less frequent with pembrolizumab than with chemotherapy (73.4% vs. 90.0%).

A phase III open-label study (KEYNOTE-024) randomly assigned 305 patients with previously untreated, advanced NSCLC with PD-L1 expression on 50% or more tumor cells and no sensitizing EGFR variants or ALK translocations to either intravenous pembrolizumab (200 mg every 3 weeks for up to 35 cycles) or platinum-based chemotherapy (four to six cycles, investigator’s choice; pemetrexed maintenance was allowed for nonsquamous tumors).[89] The primary end point was PFS. › Adverse events (any grade) were less frequent with pembrolizumab than with chemotherapy (73.4% vs. 90.0%).

Grade 3 to 5 adverse events occurred in 26.6% of patients treated with pembrolizumab and 53.3% of patients treated with chemotherapy.

A phase III open-label study (KEYNOTE-024) randomly assigned 305 patients with previously untreated, advanced NSCLC with PD-L1 expression on 50% or more tumor cells and no sensitizing EGFR variants or ALK translocations to either intravenous pembrolizumab (200 mg every 3 weeks for up to 35 cycles) or platinum-based chemotherapy (four to six cycles, investigator’s choice; pemetrexed maintenance was allowed for nonsquamous tumors).[89] The primary end point was PFS. › Adverse events (any grade) were less frequent with pembrolizumab than with chemotherapy (73.4% vs. 90.0%).

Grade 3 or 4 immune-related events occurred in 9.7% of patients treated with pembrolizumab and 0.7% of patients treated with chemotherapy.

A phase III open-label study (KEYNOTE-024) randomly assigned 305 patients with previously untreated, advanced NSCLC with PD-L1 expression on 50% or more tumor cells and no sensitizing EGFR variants or ALK translocations to either intravenous pembrolizumab (200 mg every 3 weeks for up to 35 cycles) or platinum-based chemotherapy (four to six cycles, investigator’s choice; pemetrexed maintenance was allowed for nonsquamous tumors).[89] The primary end point was PFS. › Adverse events (any grade) were less frequent with pembrolizumab than with chemotherapy (73.4% vs. 90.0%).

The most common grade 3 or 4 immune-related events associated with pembrolizumab were severe skin reactions (3.9%), pneumonitis (2.6%), and colitis (1.3%).

A phase III open-label study (KEYNOTE-024) randomly assigned 305 patients with previously untreated, advanced NSCLC with PD-L1 expression on 50% or more tumor cells and no sensitizing EGFR variants or ALK translocations to either intravenous pembrolizumab (200 mg every 3 weeks for up to 35 cycles) or platinum-based chemotherapy (four to six cycles, investigator’s choice; pemetrexed maintenance was allowed for nonsquamous tumors).[89] The primary end point was PFS. › Adverse events (any grade) were less frequent with pembrolizumab than with chemotherapy (73.4% vs. 90.0%).

There were no grade 5 immune-related events.

A phase III open-label study (KEYNOTE-024) randomly assigned 305 patients with previously untreated, advanced NSCLC with PD-L1 expression on 50% or more tumor cells and no sensitizing EGFR variants or ALK translocations to either intravenous pembrolizumab (200 mg every 3 weeks for up to 35 cycles) or platinum-based chemotherapy (four to six cycles, investigator’s choice; pemetrexed maintenance was allowed for nonsquamous tumors).[89] The primary end point was PFS.

Pembrolizumab treatment demonstrated significant improvement in PFS, OS, and DOR with less frequent adverse events compared with chemotherapy treatment.[89][Level of evidence B1]

A phase III open-label study (KEYNOTE-042 [NCT02220894]) included patients with locally advanced or metastatic NSCLC without EGFR or ALK alterations and with a PD-L1 TPS score of greater than 1%. Patients were randomly assigned to receive either pembrolizumab 200 mg once every 3 weeks for 35 cycles or chemotherapy (carboplatin plus paclitaxel or pemetrexed) for four to six cycles with optional maintenance pemetrexed (pembrolizumab, n = 637; chemotherapy, n = 637). The primary end points were OS in the populations with a PD-L1 TPS greater than 50%, greater than 20%, and greater than 1%.[93]

A phase III open-label study (KEYNOTE-042 [NCT02220894]) included patients with locally advanced or metastatic NSCLC without EGFR or ALK alterations and with a PD-L1 TPS score of greater than 1%. Patients were randomly assigned to receive either pembrolizumab 200 mg once every 3 weeks for 35 cycles or chemotherapy (carboplatin plus paclitaxel or pemetrexed) for four to six cycles with optional maintenance pemetrexed (pembrolizumab, n = 637; chemotherapy, n = 637). The primary end points were OS in the populations with a PD-L1 TPS greater than 50%, greater than 20%, and greater than 1%.[93]

The median follow-up was 61.1 months (range, 50.0–76.3).

A phase III open-label study (KEYNOTE-042 [NCT02220894]) included patients with locally advanced or metastatic NSCLC without EGFR or ALK alterations and with a PD-L1 TPS score of greater than 1%. Patients were randomly assigned to receive either pembrolizumab 200 mg once every 3 weeks for 35 cycles or chemotherapy (carboplatin plus paclitaxel or pemetrexed) for four to six cycles with optional maintenance pemetrexed (pembrolizumab, n = 637; chemotherapy, n = 637). The primary end points were OS in the populations with a PD-L1 TPS greater than 50%, greater than 20%, and greater than 1%.[93]

OS outcomes favored pembrolizumab versus chemotherapy, regardless of the PD-L1 TPS.

A phase III open-label study (KEYNOTE-042 [NCT02220894]) included patients with locally advanced or metastatic NSCLC without EGFR or ALK alterations and with a PD-L1 TPS score of greater than 1%. Patients were randomly assigned to receive either pembrolizumab 200 mg once every 3 weeks for 35 cycles or chemotherapy (carboplatin plus paclitaxel or pemetrexed) for four to six cycles with optional maintenance pemetrexed (pembrolizumab, n = 637; chemotherapy, n = 637). The primary end points were OS in the populations with a PD-L1 TPS greater than 50%, greater than 20%, and greater than 1%.[93] › OS outcomes favored pembrolizumab versus chemotherapy, regardless of the PD-L1 TPS.

The HR was 0.68 (95% CI, 0.57–0.81) for the TPS >50% group, 0.75 (95% CI, 0.64–0.87) for the TPS >20% group, and 0.79 (95% CI, 0.70–0.89) for the TPS >1% group.

A phase III open-label study (KEYNOTE-042 [NCT02220894]) included patients with locally advanced or metastatic NSCLC without EGFR or ALK alterations and with a PD-L1 TPS score of greater than 1%. Patients were randomly assigned to receive either pembrolizumab 200 mg once every 3 weeks for 35 cycles or chemotherapy (carboplatin plus paclitaxel or pemetrexed) for four to six cycles with optional maintenance pemetrexed (pembrolizumab, n = 637; chemotherapy, n = 637). The primary end points were OS in the populations with a PD-L1 TPS greater than 50%, greater than 20%, and greater than 1%.[93] › OS outcomes favored pembrolizumab versus chemotherapy, regardless of the PD-L1 TPS.

The OS rates for patients who received pembrolizumab were 21.9% (TPS >50%), 19.4% (TPS >1%), and 16.6% (TPS >1%).

A phase III open-label study (KEYNOTE-042 [NCT02220894]) included patients with locally advanced or metastatic NSCLC without EGFR or ALK alterations and with a PD-L1 TPS score of greater than 1%. Patients were randomly assigned to receive either pembrolizumab 200 mg once every 3 weeks for 35 cycles or chemotherapy (carboplatin plus paclitaxel or pemetrexed) for four to six cycles with optional maintenance pemetrexed (pembrolizumab, n = 637; chemotherapy, n = 637). The primary end points were OS in the populations with a PD-L1 TPS greater than 50%, greater than 20%, and greater than 1%.[93]

The most common adverse reactions reported in at least 10% of patients who received pembrolizumab as a single agent in KEYNOTE-042 included fatigue, decreased appetite, dyspnea, cough, rash, constipation, diarrhea, nausea, hypothyroidism, pneumonia, pyrexia, and weight loss.