KEYNOTE-042: Pembrolizumab Improved Overall Survival in Non-Small Cell Lung Cancer

CHICAGO—Pembrolizumab led to superior overall survival (OS) among patients with previously untreated advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR or ALK mutations and PD-L1 tumor proportion score (TPS) greater than or equal to 1% over platinum-based chemotherapy regimens, according to data presented during the Plenary Session at the American Society of Clinical Oncology 2018 Annual Meeting on Sunday, June 3.¹

Data from the KEYNOTE-024 study previously demonstrated that first-line pembrolizumab therapy led to significantly prolonged progression-free survival (PFS) and OS among patients with metastatic NSCLC. Study participants had no targetable alterations and a PD-L1 TPS greater than or equal to 50% in KEYNOTE-024, but in KEYNOTE-042 (ClinicalTrials.gov Identifier: NCT02220894), authors evaluated the efficacy of pembrolizumab among patients with lower TPS of 1% or more.

In this phase 3 study, researchers randomly assigned 1274 patients to receive pembrolizumab 200 mg every 3 weeks or investigator’s choice chemotherapy, including: paclitaxel plus carboplatin, or pemetrexed plus carboplatin with optional pemetrexed maintenance therapy for nonsquamous histology only.

Overall, 637 patients were assigned to each arm and 47.0% (599) and 64.2% (818) had TPS greater than or equal to 50% and greater than or equal to 20%, respectively. The median follow-up was 12.8 months.

At the time of analysis, 13.7% of patients in the pembrolizumab arm were continuing therapy versus 4.9% of patients who were receiving pemetrexed maintenance therapy.

OS was significantly improved among patients with TPS 50% or more treated with pembrolizumab with 20.0 months compared with 12.2 months among patients who received chemotherapy (hazard ratio [HR], 0.69; 95% CI, 0.56-0.85; P = .0003). Among patients with TPS 20% or more, pembrolizumab led to OS of 17.7 months versus 13.0 months in the chemotherapy arm (HR, 0.77; 95% CI, 0.64-0.92; P = .0020). Among patients with TPS 1% or more, patients in the pembrolizumab arm had an OS of 16.7 months compared with 12.1 months among patients treated with chemotherapy (HR, 0.81; 95% CI, 0.71-0.93; P = .0018).

Moreover, patients receiving pembrolizumab experienced a lower rate of treatment-related grade 3 to 5 adverse events compared with chemotherapy (17.8% vs 41.0%).

PFS outcomes are still under investigation.

The authors concluded that “these data confirm and potentially extend the role of pembrolizumab monotherapy as a standard first-line treatment for PD-L1-expressing advanced/metastatic NSCLC.”

Read more of Cancer Therapy Advisor‘s coverage of the American Society of Clinical Oncology (ASCO) 2018 meeting by visiting the conference page.

Reference

1. Lopes G, Wu YL, Kudaba I, et al. Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 1%: Open-label, phase 3 KEYNOTE-042 study. Late breaking abstract presentation at: 2018 ASCO Annual Meeting; June 1-5, 2018; Chicago, IL.