As reported in the Journal of Clinical Oncology by Marina C. Garassino, MD, and colleagues, 5-year follow-up in the phase III KEYNOTE-189 trial has shown maintained progression-free and overall survival benefits with the addition of pembrolizumab to pemetrexed and platinum chemotherapy in the first-line treatment of patients with metastatic nonsquamous non–small cell lung cancer (NSCLC) without EGFR or ALK alterations.
The trial supported the August 2018 approval of pembrolizumab in combination with pemetrexed and platinum chemotherapy as first-line treatment for patients with metastatic nonsquamous NSCLC with no EGFR or ALK genomic tumor aberrations.
Marina C. Garassino, MD
Study Details
In the double-blind trial, 616 patients were randomly assigned 2:1 to receive pembrolizumab at 200 mg (n = 410) or placebo (n = 206) every 3 weeks for up to 35 cycles in combination with pemetrexed and investigator’s choice of carboplatin or cisplatin for four cycles, followed by maintenance pemetrexed until disease progression or unacceptable toxicity. Patients in the control group were permitted to cross over to receive pembrolizumab monotherapy upon disease progression.
The primary endpoints were progression-free survival on blinded independent central review and overall survival. In the initial report from the trial, the pembrolizumab group had significantly better progression-free (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.43–0.64, P < .001) and overall survival (HR = 0.49, 95% CI = 0.38–0.64, P < .001) vs the control group.
Key Findings
In the current analysis, median time from random assignment to data cutoff (in March 2022) was 64.6 months (range = 60.1–72.4 months). The pembrolizumab group showed significantly better progression-free survival vs the control group (HR = 0.50, 95% CI = 0.42–0.60). Rates at 5 years were 7.5% vs 0.6%.
Among patients in the pembrolizumab group, 224 (54.6%) received subsequent anticancer therapy, with 103 (25.1%) receiving anti–PD-1/PD-L1 therapy. In the control group, 84 patients (40.8%) crossed over to receive pembrolizumab monotherapy on-study and an additional 34 received anti–PD-1/PD-L1 therapy outside the study (effective crossover rate = 57.3%).
The pembrolizumab group showed significantly better overall survival vs the control group (HR = 0.60, 95% CI = 0.50–0.72); rates at 5 years were 19.4% vs 11.3%. Similar trends in progression-free and overall survival were observed across all PD-L1 tumor proportion score subgroups.
Among 57 patients in the pembrolizumab group who completed 35 cycles of pembrolizumab, the objective response rate was 86.0%, and 3-year overall survival after completing 35 cycles (approximately 5 years after random assignment) was 71.9%.
The investigators concluded, “Pembrolizumab plus pemetrexed/platinum maintained overall survival and progression-free survival benefits vs placebo plus pemetrexed/platinum, regardless of PD-L1 expression. These data continue to support pembrolizumab plus pemetrexed/platinum as a standard of care in previously untreated [patients] with metastatic NSCLC without EGFR/ALK alterations.”
Dr. Garassino, of the Knapp Center for Biomedical Discovery, University of Chicago Medicine & Biological Sciences, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit ascopubs.org.
