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 (ClinicalTrials.gov 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.
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 (ClinicalTrials.gov 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.
- 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. https://investor.lilly.com/releasedetail.cfm?ReleaseID=992751. Updated October 9, 2016. Accessed October 31, 2016.