Pembrolizumab plus chemotherapy

A phase III double-blind trial (KEYNOTE-189 [NCT02578680]) randomly assigned, in a 2:1 ratio, 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR variants or ALK rearrangements who had received no previous treatment for metastatic disease. Patients received pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance.[1] Crossover to pembrolizumab monotherapy was permitted after verified progression among patients in the placebo-containing combination group. The primary end points were OS and PFS as assessed by blinded independent central committee radiological review.

A phase III double-blind trial (KEYNOTE-189 [NCT02578680]) randomly assigned, in a 2:1 ratio, 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR variants or ALK rearrangements who had received no previous treatment for metastatic disease. Patients received pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance.[1] Crossover to pembrolizumab monotherapy was permitted after verified progression among patients in the placebo-containing combination group. The primary end points were OS and PFS as assessed by blinded independent central committee radiological review.

In the 5-year updated analysis, the median time from random assignment to data cutoff was 64.6 months (range, 60.1–72.4).[90]

A phase III double-blind trial (KEYNOTE-189 [NCT02578680]) randomly assigned, in a 2:1 ratio, 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR variants or ALK rearrangements who had received no previous treatment for metastatic disease. Patients received pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance.[1] Crossover to pembrolizumab monotherapy was permitted after verified progression among patients in the placebo-containing combination group. The primary end points were OS and PFS as assessed by blinded independent central committee radiological review.

After 5 years, pembrolizumab plus pemetrexed-platinum was associated with improved OS and PFS, compared with placebo plus pemetrexed-platinum in patients with metastatic nonsquamous NSCLC, regardless of PD-L1 expression. In the ITT population, 5-year OS rates were 19.4% in the pembrolizumab plus pemetrexed-platinum group, compared with 11.3% in the placebo plus pemetrexed-platinum group.

A phase III double-blind trial (KEYNOTE-189 [NCT02578680]) randomly assigned, in a 2:1 ratio, 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR variants or ALK rearrangements who had received no previous treatment for metastatic disease. Patients received pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance.[1] Crossover to pembrolizumab monotherapy was permitted after verified progression among patients in the placebo-containing combination group. The primary end points were OS and PFS as assessed by blinded independent central committee radiological review.

Survival was higher in patients with a higher PD-L1 tumor proportion score (TPS), especially in the TPS >50% subgroup (29.6% vs. 21.4%).

A phase III double-blind trial (KEYNOTE-189 [NCT02578680]) randomly assigned, in a 2:1 ratio, 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR variants or ALK rearrangements who had received no previous treatment for metastatic disease. Patients received pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance.[1] Crossover to pembrolizumab monotherapy was permitted after verified progression among patients in the placebo-containing combination group. The primary end points were OS and PFS as assessed by blinded independent central committee radiological review.

There were 57 patients who completed 35 cycles of pembrolizumab. For these patients, the objective response rate was 86.0% and the 3-year OS rate after completing 35 cycles (approximately 5 years after random assignment) was 71.9%.[90]

A phase III double-blind trial (KEYNOTE-189 [NCT02578680]) randomly assigned, in a 2:1 ratio, 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR variants or ALK rearrangements who had received no previous treatment for metastatic disease. Patients received pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance.[1] Crossover to pembrolizumab monotherapy was permitted after verified progression among patients in the placebo-containing combination group. The primary end points were OS and PFS as assessed by blinded independent central committee radiological review.

Immune-mediated adverse events and infusion reactions occurred in 113 (27.9%) and 27 (13.4%) patients.

A phase III double-blind trial (KEYNOTE-189 [NCT02578680]) randomly assigned, in a 2:1 ratio, 616 patients with metastatic nonsquamous NSCLC without sensitizing EGFR variants or ALK rearrangements who had received no previous treatment for metastatic disease. Patients received pemetrexed and a platinum-based drug plus either 200 mg of pembrolizumab or placebo every 3 weeks for 4 cycles, followed by pembrolizumab or placebo for up to a total of 35 cycles plus pemetrexed maintenance.[1] Crossover to pembrolizumab monotherapy was permitted after verified progression among patients in the placebo-containing combination group. The primary end points were OS and PFS as assessed by blinded independent central committee radiological review.

Adverse events of grade 3 or higher occurred with similar frequency in both treatment groups (71.9% in the pembrolizumab combination group vs. 66.8% in the placebo combination group).

A phase III, randomized, double-blind study (KEYNOTE-407 [NCT02775435]) included previously untreated patients with metastatic squamous cell NSCLC. Patients were randomly assigned 1:1 to receive pembrolizumab 200 mg or placebo plus carboplatin and paclitaxel/nab-paclitaxel once every 3 weeks for four cycles, followed by pembrolizumab or placebo for up to 35 cycles (pembrolizumab-plus-chemotherapy, n = 5,278; placebo-plus-chemotherapy, n = 5,281). Primary end points were OS and PFS per RECIST version 1.1 by blinded independent central review.[91]

A phase III, randomized, double-blind study (KEYNOTE-407 [NCT02775435]) included previously untreated patients with metastatic squamous cell NSCLC. Patients were randomly assigned 1:1 to receive pembrolizumab 200 mg or placebo plus carboplatin and paclitaxel/nab-paclitaxel once every 3 weeks for four cycles, followed by pembrolizumab or placebo for up to 35 cycles (pembrolizumab-plus-chemotherapy, n = 5,278; placebo-plus-chemotherapy, n = 5,281). Primary end points were OS and PFS per RECIST version 1.1 by blinded independent central review.[91]

The median time from random assignment to data cutoff was 56.9 months (range, 49.9–66.2). OS and PFS were improved with pembrolizumab-plus-chemotherapy versus placebo-plus-chemotherapy (HR, 0.71 [0.59–0.85] and 0.62 [0.52–0.74]), respectively; 95% CI). The 5-year OS rates were 18.4% and 9.7%, respectively.[91][Level of evidence A1]

A phase III, randomized, double-blind study (KEYNOTE-407 [NCT02775435]) included previously untreated patients with metastatic squamous cell NSCLC. Patients were randomly assigned 1:1 to receive pembrolizumab 200 mg or placebo plus carboplatin and paclitaxel/nab-paclitaxel once every 3 weeks for four cycles, followed by pembrolizumab or placebo for up to 35 cycles (pembrolizumab-plus-chemotherapy, n = 5,278; placebo-plus-chemotherapy, n = 5,281). Primary end points were OS and PFS per RECIST version 1.1 by blinded independent central review.[91]

A total of 55 patients completed 35 cycles of pembrolizumab. The objective response rate was 90.9% and the 3-year OS rate after completion of 35 cycles (approximately 5 years after random assignment) was 69.5%.