Pembrolizumab represents a new standard initial treatment to offer patients with advanced/metastatic non–small-cell lung cancer (NSCLC) and programmed death ligand 1 (PD-L1)-expression of 1% or more, results of the large, randomized phase III KEYNOTE-042 trial suggest. The findings were discussed in a plenary session (abstract LBA4) during the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.
Presented by Gilberto Lopes, MD, MBA, from Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, Florida, the study results showed patients with PD-L1 expression of 1% or more who were first treated with pembrolizumab immunotherapy lived a median of 4 to 8 months longer than those treated with chemotherapy. In addition, severe side effects occurred in fewer patients receiving pembrolizumab (18%), compared with those treated with chemotherapy (41).
“A large number of patients with lung cancer now have a new treatment option with better efficacy and fewer side effects than standard chemotherapy,” Dr. Lopes said.
Based on findings from a previous, smaller clinical trial (KEYNOTE-024), the US Food and Drug Administration had already approved pembrolizumab for initial treatment of NSCLC with high PD-L1 expression (score of at least 50%), as a stand-alone treatment and in combination with chemotherapy.
In the current study, researchers randomly assigned 1,274 patients with locally advanced or metastatic NSCLC to receive pembrolizumab or one of two standard-of-care therapies: carboplatin plus either paclitaxel or pemetrexed. Both squamous and nonsquamous cancers were included in the trial. However, patients were excluded if they could be treated with EGFR (epidermal growth factor receptor) inhibitors and ALK inhibitors.
The researchers evaluated responses in three patient groups: patients with at least 50% PD-L1 expression (n = 599), those with at least 20% PD-L1 expression (n = 818), and those with at least 1% PD-L1 expression (N = 1,274). Equal numbers of patients in each PD-L1 expression group received pembrolizumab and chemotherapy. The median follow-up time was 12.8 months. Compared with patients receiving standard chemotherapy, patients who received pembrolizumab had a longer median overall survival (OS), regardless of PD-L1 expression in the tumor.
The study showed that the benefit of pembrolizumab was greater when the level of PD-L1 expression was higher. For patients with PD-L1 expression of 50% or more, the OS was 20 months with pembrolizumab vs 12.2 months with chemotherapy. For patients with PD-L1 expression of 20% or more, the OS was 17.7 months with pembrolizumab vs 13 months with chemotherapy. For patients with PD-L1 expression of 1% or more, the OS was 16.7 months with pembrolizumab vs 12.1 months with chemotherapy.
At this time, it is not yet clear whether pembrolizumab combined with chemotherapy is better than pembrolizumab alone in patients who express PD-L1. Ongoing research is exploring the adjuvant use of pembrolizumab and combinations of immunotherapy with bevacizumab-containing combination regimens as part of initial therapy for NSCLC.
ASCO Expert John Heymach, MD, PhD, Chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, Houston, said it appears that immunotherapy with pembrolizumab alone benefits a much larger number of patients than had been previously thought. “This is yet another promising result with immunotherapy in lung cancer that brings new momentum to the treatment of this notoriously difficult disease,” Dr. Heymach said.