Lung cancer was considered a poorly immunogenic malignancy; recent strategies targeting checkpoints of the immune system, however, show significant anti-tumor activity in previously treated advanced non-small cell lung cancer (NSCLC). Two agents targeting the programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis are approved by the U.S. Food and Drug Administration for patients with previously treated advanced NSCLC.
Justin F. Gainor, MD, of Massachusetts General Hospital in Boston, and colleagues recently published a review of immune checkpoint inhibitors in NSCLC in The Oncologist.1 Cancer Therapy Advisor spoke with Dr Gainor to discuss progress to date and future directions of immune checkpoint inhibition for patients with NSCLC.
Targeting PD-1
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There are 2 FDA-approved PD-1 inhibitors for NSCLC. Nivolumab (Bristol-Myers Squibb) was approved in October 2015 based on data from 2 phase 3 trials. CheckMate 017 (ClinicalTrials.gov Identifier: NCT01642004) included 272 patients; each was randomly assigned to nivolumab or docetaxel. The trial was stopped early when an interim analysis showed that patients assigned nivolumab had significantly improved overall survival in contrast with docetaxel. Patients assigned nivolumab had significantly improved progression-free survival.
In CheckMate 057 (ClinicalTrials.gov Identifier: NCT01673867), a companion study, 582 patients were randomly assigned to nivolumab or docetaxel. This trial was also stopped early when an interim analysis showed that nivolumab significantly improved overall survival.
In October 2016, The FDA approved pembrolizumab for patients with previously treated NSCLC whose tumors expressed PD-L1. The efficacy of pembrolizumab was evaluated in the phase 1 KEYNOTE-001 (ClinicalTrials.gov Identifier: NCT01295827) trial, in which 495 patients were enrolled. Researchers used a cutoff of PD-L1 expression on 50% of more tumor cells; among patients with that level of PD-L1 expression, the overall response rate ranged from 36.6% to 45.2%.
The phase 3 KEYNOTE-010 (ClinicalTrials.gov Identifier: NCT01905657) trial required patients to have PD-L1 expression on at least 1% of tumor cells. This trial showed that pembrolizumab significantly improved overall survival in contrast with docetaxel, but no difference in progression-free survival was found.
