In an analysis reported in Annals of Oncology, Roy S. Herbst, MD, PhD, and colleagues found that pembrolizumab was active in both KRAS-mutant and wild-type tumors in a subgroup of patients in the KEYNOTE-042 trial with programmed cell death ligand 1 (PD-L1)-positive nonsquamous non–small cell lung cancer (NSCLC). The phase III trial showed that first-line pembrolizumab improved overall survival vs platinum-based chemotherapy among all patients with PD-L1–positive (tumor proportion score ≥ 1%) NSCLC.
These data were also presented at the European Society for Medical Oncology Immuno-Oncology Congress 2019.
“Findings of this descriptive exploratory analysis suggest that pembrolizumab monotherapy vs chemotherapy alone was generally associated with improved clinical outcomes regardless of KRAS status in advanced nonsquamous NSCLC.”— Roy S. Herbst, MD, PhD, and colleagues
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Among 782 patients in the trial with nonsquamous disease, whole-exome sequencing data on KRAS mutation status was available for 301. Among these, 69 patients (23%) had KRAS mutations, including 30 in the pembrolizumab group and 39 in the chemotherapy group. No KRAS mutations were found in 127 patients in the pembrolizumab group and 105 in the chemotherapy group.
Patients with KRAS mutations exhibited higher PD-L1 tumor proportion scores (median = 60% vs 35%). Objective response rates were 56.7% among patients treated with pembrolizumab vs 18.0% among patients treated with chemotherapy with a KRAS mutation, and 29.1% vs 21.0%, respectively, among those without a KRAS mutation.
Median progression-free survival was 12 months vs 6 months (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.29–0.87) among patients with a KRAS mutation and 6 months vs 6 months (HR = 1.00, 95% CI = 0.75–1.34) among those without a KRAS mutation. Median overall survival was 28 months vs 11 months (HR = 0.42, 95% CI = 0.22–0.81) among patients with a KRAS mutation and 15 months vs 12 months (HR = 0.86, 95% CI = 0.63–1.18) among those without a KRAS mutation.
The investigators concluded, “Findings of this descriptive exploratory analysis suggest that pembrolizumab monotherapy vs chemotherapy alone was generally associated with improved clinical outcomes regardless of KRAS status in advanced nonsquamous NSCLC…. These findings also suggest that a pembrolizumab-containing regimen is a clinically relevant comparator for studies of KRAS-targeted therapy given as first-line treatment of NSCLC.” ■
Disclosure: For full disclosures of the study authors, visit academic.oup.com.