Pembrolizumab Bests Chemotherapy in PD-L1–Expressing NSCLC


Pembrolizumab represents a new standard first-line treatment option for PD-L1–expressing advanced/metastatic NSCLC, according to KEYNOTE-042 investigators.

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.



Recent Videos
Advocacy groups such as Cancer Support Community and the Leukemia & Lymphoma Society may help support patients with CML undergoing treatment.
Paolo Tarantino, MD, discusses the potential utility of agents such as datopotamab deruxtecan and enfortumab vedotin in patients with breast cancer.
Paolo Tarantino, MD, highlights strategies related to screening and multidisciplinary collaboration for managing ILD in patients who receive T-DXd.
Those with CML should discuss adverse effects such as nausea or fatigue with their providers to help optimize their quality of life during treatment.
Patients with CML can become an active part of their treatment plan by discussing any questions that come to mind with their providers.
Jorge E. Cortes, MD, emphasizes proper communication between patients with chronic myeloid leukemia and their providers during the treatment course.
Dietary interventions or other medications may help mitigate diarrhea in patients who undergo therapy for chronic myeloid leukemia.
Considering notable adverse effects associated with treatment may be critical when selecting therapy options for those with CML.
Byoung Chul Cho, MD, PhD, highlights ongoing trials assessing intravenous and subcutaneous amivantamab in EGFR-mutant non–small cell lung cancer.
An AI-based system may reduce the time needed to match patients with cancer to suitable clinical trials.
Related Content