Pooled data on two clinical trials demonstrated patients with previously treated non–small cell lung cancer (NSCLC) treated with nivolumab had a greater than fivefold increase in 5-year overall survival rate compared to treatment with the chemotherapy docetaxel. Scott Gettinger, MD, of Yale Comprehensive Cancer Center, presented these results at the International Association for the Study of Lung Cancer (IASLC) 2019 World Conference on Lung Cancer (WCLC) (Abstract OA14.04).

Scott Gettinger, MD

Historically, outcomes for patients with advanced NSCLC have been poor, with 5-year survival rates at less than 5% after treatment with conventional chemotherapy. Nivolumab was approved by the U.S. Food and Drug Administration in 2015 for patients with previously treated, advanced NSCLC based on results from two randomized phase III trials—CheckMate 017 and CheckMate 057—which demonstrated improved overall survival compared to docetaxel.

Methods

In CheckMate 017 and 057, 854 patients with advanced NSCLC, Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1, and disease progression during or after first-line platinum-based chemotherapy were randomly assigned 1:1 to nivolumab or docetaxel until disease progression or unacceptable toxicity. After completion of the primary analyses, patients in the docetaxel arm no longer receiving benefit could cross over to receive nivolumab. The researchers set overall survival as the primary endpoint for both studies.

5-Year Follow-up

At 5-year follow-up, 50 patients in the nivolumab arm and 9 patients in the docetaxel arm were alive. Baseline characteristics of 5-year survivors in both arms were similar to the overall population and patients who survived less than 1 year, except for a higher percentage of patients with ECOG PS 0 or tumor programmed cell death ligand 1 (PD-L1) expression > 1% treated with nivolumab, and ECOG PS 0 and stage IIIB NSCLC treated with docetaxel. Nivolumab continued to show long-term overall survival and progression-free survival benefit compared to docetaxel, with 5-year survival rates of 13.4% vs 2.6% and progression-free survival rates of 8% vs 0%. The overall survival benefit with nivolumab compared with docetaxel was observed across subgroups, including patients with tumor PD-L1 expression < 1%.

No new safety signals were observed with longer follow-up. Between 3- and 5-year follow-up, 8 of the 31 patients treated with nivolumab (26%) reported a treatment-related adverse event, and 1 patient (3%) reported a grade 3 or 4 event. The most common select adverse events (events with a potential immunologic cause) were related to skin in four patients (13%), and none were grade 3 or 4.

“CheckMate 017 and 057 are the first phase III trials to report 5-year outcomes for a [programmed cell death protein 1] inhibitor in previously treated advanced NSCLC, demonstrating a greater than fivefold increase in 5-year overall survival rates with nivolumab (13.4%) compared with docetaxel (2.6%). Nivolumab remained well tolerated, with no new safety signals [reported],” concluded Dr. Gettinger.

Disclosure: For full disclosures of the study authors, visit wclc2019.iaslc.org.