Updated trial results support the use of frontline pembrolizumab plus pemetrexed and platinum chemotherapy as standard care for patients with metastatic non-small cell lung cancer (NSCLC) without EGFR/ALK alterations, according to researchers. These results were published in the Journal of Clinical Oncology.
At 5 years, patients who received pembrolizumab plus pemetrexed and platinum chemotherapy had better overall survival (OS) and progression-free survival (PFS) than patients who received placebo plus pemetrexed-platinum chemotherapy, regardless of PD-L1 status.
This phase 3 trial (KEYNOTE-189; ClinicalTrials.gov Identifier: NCT02578680) included 616 patients with previously untreated, metastatic NSCLC without EGFR/ALK mutations. They were randomly assigned to receive pembrolizumab plus pemetrexed-platinum chemotherapy (n=410) or placebo plus pemetrexed-platinum chemotherapy (n=206).
Patients received pembrolizumab (200 mg) once every 3 weeks for up to 35 cycles. They received pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (area under the curve 5 mg/mL/min) once every 3 weeks for 4 cycles, followed by pemetrexed maintenance for up to 35 cycles. Patients in the placebo arm who had progressive disease could cross over to receive pembrolizumab alone. Patients could also receive a second course of pembrolizumab alone for up to 17 cycles if they met certain criteria.
The median time from randomization to the data cutoff was 64.6 months. The OS, PFS, and second PFS (PFS2) were all significantly better in the pembrolizumab arm than in the placebo arm. Benefits with pembrolizumab were seen regardless of PD-L1 status.
The median OS was 22.0 months in the pembrolizumab arm and 10.6 months in the placebo arm (hazard ratio [HR], 0.60; 95% CI, 0.50-0.72). The 5-year OS rate was 19.4% and 11.3%, respectively.
The median PFS was 9.0 months in the pembrolizumab arm and 4.9 months in the placebo arm (HR, 0.50; 95% CI, 0.42-0.60). The 5-year PFS rate was 7.5% and 0.6%, respectively.
The median PFS2 was 17.0 months in the pembrolizumab arm and 9.1 months in the placebo arm (HR, 0.54; 95% CI, 0.45-0.65). The 5-year PFS2 rate was 16.7% and 7.8%, respectively.
Adverse events were reported in nearly all patients in the pembrolizumab arm (99.8%) and the placebo arm (99.0%). There were no new fatal adverse events.
“These results continue to support the combination of first-line pembrolizumab plus a platinum and pemetrexed as a standard of care for these patients,” the researchers concluded.
Disclosures: This research was supported by Merck Sharp & Dohme LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Garassino MC, Gadgeel S, Speranza G, et al. Pembrolizumab plus pemetrexed and platinum in nonsquamous non–small-cell lung cancer: 5-year outcomes from the phase 3 KEYNOTE-189 study. J Clin Oncol. Published online February 21, 2023. doi:10.1200/JCO.22.01989