The addition of pembrolizumab to first-line treatment with pemetrexed and carboplatin significantly improved objective response rate and progression-free survival compared with chemotherapy alone among patients with metastatic non-small cell lung cancer (NSCLC), according to findings presented at the European Society for Medical Oncology (ESMO) 2016 Congress.1

The G cohort of the open-label, multi-cohort, phase 1/2 KEYNOTE-021 study ( Identifier: NCT02039674) included 123 treatment-naive patients with advanced non-squamous NSCLC regardless of PD-L1 expression whose tumors did not harbor EGFR or ALK aberrations. Participants were randomly assigned 1:1 to receive pemetrexed plus carboplatin with or without pembrolizumab. Those who experienced disease progression while receiving chemotherapy alone were eligible to crossover to pembrolizumab monotherapy.

At a median follow-up of 10.6 months, results showed that objective response rate was 55% with pembrolizumab vs 29% with chemotherapy alone (treatment difference, 26%; 95% CI, 9-42; P = .0016). All responses were partial.

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Researchers also found that the chemoimmunotherapy combination significantly reduced the risk of progression or death by 47% compared with pemetrexed plus carboplatin (hazard ratio, 0.53; 95% CI, 0.31-0.91; P = .0102). Median progression-free-survival was 13.0 months with the 3-drug combination and 8.9 months in the control arm.

There was no significant difference in overall survival between the 2 treatment arms. The 6-month overall survival rate was 92% in both arms, and the 12-month overall survival rate was 75% and 72% in the pembrolizumab arm and chemotherapy alone arm, respectively.

The most common treatment-related adverse events in the chemoimmunotherapy arm were fatigue, nausea, anemia, rash, vomiting, diarrhea, increased aspartate transaminase (AST), constipation, decreased appetite, increased alanine transaminase (ALT), dysgeusia, and neutropenia. Grade 3 to 4 treatment-related adverse events in this arm included fatigue, nausea, anemia, rash, vomiting, increased AST, increased ALT, and neutropenia. The rate of immune-mediated adverse events was similar to that observed with single-agent pembrolizumab.

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The phase 3 KEYNOTE-189 trial ( Identifier: NCT02578680) will evaluate the combination of pemetrexed, pembrolizumab, and a platinum agent (cisplatin or carboplatin) compared with chemotherapy only as initial therapy among patients with NSCLC.                       


  1. New data on the combination of Lilly’s Alimta (pemetrexed) and Merck’s Keytruda (pembrolizumab) show a near-doubling of objective response rate compared to standard of care alone in first-line metastatic non-small cell lung cancer. Eli Lilly and Company website. Updated October 9, 2016. Accessed October 31, 2016.