Nivolumab for Advanced Nonsquamous Non–Small-Cell Lung Cancer

Summary and Comment |
October 9, 2015

Nivolumab for Advanced Nonsquamous Non–Small-Cell Lung Cancer

  1. Anne S. Tsao, MD

Overall survival was longer with nivolumab versus docetaxel in NSCLC patients, especially those with tumor PD-L1 expression.

  1. Anne S. Tsao, MD

Immunotherapies are a new class of agents used in non–small-cell lung cancer (NSCLC) that require refinement of the optimal sequence and identification of the right target population of patients. Now, investigators have conducted an industry-supported, phase III, international, randomized, open-label trial to evaluate the efficacy and safety of nivolumab, a human IgG4 programmed death 1 (PD-1) immune checkpoint inhibitor antibody, versus docetaxel in 582 nonsquamous NSCLC patients who progressed after one or two lines of therapy (including a platinum-doublet).

Overall survival (OS; the primary endpoint) was improved with nivolumab versus docetaxel (12.2 vs. 9.4 months; hazard ratio, 0.73; P=0.002) as were response rates (19% vs. 12%; P=0.02). However, the median progression-free survival (PFS) trended longer with docetaxel (4.2 vs. 2.3 months). In a subgroup analysis, nivolumab improved OS across most subgroups, except in never smokers, third-line patients, those with central nervous system metastases, EGFR-mutation positive patients, and rest-of-world geography (South America, Asia, Australia).

Adverse events were less frequent with nivolumab versus docetaxel (10% vs. 54%). The most frequent nivolumab adverse events were fatigue (16%), nausea (12%), decreased appetite (10%), and asthenia (10%); pneumonitis occurred in 1% of nivolumab-treated patients and was the most common toxicity leading to treatment discontinuation. PD-L1 immunohistochemistry levels were evaluated in archived tissue and were balanced between the two treatment arms. PD-L1 positivity was predictive for an improved outcome across all efficacy endpoints with nivolumab versus docetaxel. Patients with no PD-L1 tumor expression experienced similar OS with nivolumab or docetaxel.


This study raises some concern that PD-L1 positivity should be assessed in nonsquamous NSCLC patients, especially if they are never-smokers or carry EGFR mutations. Proponents for nivolumab point out that there was no difference in survival in PD-L1–negative patients but that the lower toxicity rate with nivolumab should still justify its use. However, it is important to note that docetaxel had a higher PFS benefit. Future research investigation is needed to optimize therapy for the patients who did not have OS benefit to nivolumab.

Editor Disclosures at Time of Publication

  • Disclosures for Anne S. Tsao, MD at time of publication Consultant / Advisory board Genetech; Roche; Medimmune; Novartis; Astellas; Boehringer-Ingelheim; Eli Lilly Speaker’s bureau Genetech; Roche; Medimmune; Novartis; Astellas; Boehringer-Ingelheim; Eli Lilly Grant / Research support Department of Defense; SWOG Leadership positions in professional societies American Medical Association (Member); American Association of Cancer Research (Member); American Society of Clinical Oncology (Member); AACR-Women in Cancer Research (Member); International Mesothelioma Interest Group (Member); SWOG (Member); International Association for the Study of Lung Cancer (Communications Committee Chair); American Radium Society (Chair); RTOG (Member)


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