LONG TERM SURVIVAL WITH NIVOLUMAB FOR NSCLC

New data from clinical trials that led to the approval of immunotherapy with nivolumab (Opdivo, Bristol-Myers Squibb) in nonsmall cell lung cancer (NSCLC) now show that patients who respond to the drug have better survival in the longer term.

More than half (58%) of such patients were still alive after 4 years, whereas the historical survival of patients with advanced NSCLC has been 5% at 5 years.    

The data are from the CheckMate-017 and CheckMate-057 studies, which compared nivolumab with docetaxel, both used as monotherapy.

In a pooled analysis of the two studies, 4-year overall survival (OS) for all patients was 14% with nivolumab vs 5% with docetaxel.

However, among the subset of patients who had a complete response (CR) or partial response (PR) at 6 months after treatment, the 4-year OS was 58% for nivolumab vs 12% for docetaxel.

These data were presented at the American Association of Cancer Research (AACR) 2019 Annual Meeting.

"These analyses in a large population of patients with previously treated advanced NSCLC show, for the first time, that response to nivolumab correlates to a survival benefit over many years," senior author Scott Antonia, MD, PhD, director of the Duke Cancer Institute, Center for Cancer Immunotherapy, Durham, North Carolina, said in a company statement.

"These long-term survival outcomes are particularly interesting given that, historically, the average 5-year survival rate for this patient population is approximately 5%," he added.

Study Details

Although the analysis also included patients from two open-label phase 1 and phase 2 studies, the pooled analysis of CheckMate-017 and CheckMate-057 is the longest follow-up from phase 3 randomized trials of previously treated advanced NSCLC.

Minimum follow-up for this analysis was 51.6 months.

The 854 patients across the two studies were approximately 62 years of age, 38% were women, 31% had NSCLC of squamous histology, and 42% had program cell death ligand 1 (PD-L1) expression ≥ 1% (PD-L1 < 1%, 37%).

Median OS was 11.1 months for patients receiving nivolumab (n = 427) vs 8.1 months for patients receiving docetaxel.

OS rates for nivolumab vs docetaxel were 48% vs 34% at 1 year, 27% vs 14% at 2 years, and 17% vs 8% at 3 years.

OS rates were marginally higher for patients who had PD-L1 ≥ 1% and received nivolumab.

However, survival rates were considerably higher when the analysis was restricted to patients who had shown good responses. For patients who achieved CR or PR at 6 months, the OS rate for nivolumab vs docetaxel was 81% vs 62% at 1 year, 63% vs 38% at 2 years, and 61% vs 26% at 3 years.

In addition, survival rates were also higher for patients who had stable disease 6 months after treatment. In this subgroup, the 4-year OS rate was 19% with nivolumab vs 2% for docetaxel.

Compared with patients who progressed on nivolumab, patients who achieved a response on nivolumab had an 82% relative reduced risk for death. For patients who progressed on docetaxel, achieving a CR or PR with docetaxel was associated with a 57% relative reduced risk for death.

The authors reported no new or unexpected safety signals with the long-term follow-up. The most common treatment-related adverse events that were potentially immune related were skin reactions, which occurred at an incidence rate of 38.6/100 person-years.

"These analyses...show for the first time that response to nivolumab provides a durable survival benefit that extends for many years vs docetaxel, even after disease progression," the authors concluded.

Disclosures for the authors are listed in the abstract. 

AACR 2019. Presented April 2, 2019. Abstract CT195.