Nivolumab confers fivefold OS improvement over chemotherapy in advanced NSCLC
BARCELONA, Spain — Nivolumab led to a fivefold improvement in OS at 5 years compared with docetaxel among patients with previously treated advanced non-small cell lung cancer, according to pooled results from the CheckMate 017 and 057 trials presented at International Association for the Study of Lung Cancer World Conference on Lung Cancer.
This represents the first report of 5-year OS from any randomized trial evaluating PD-1 inhibitors in lung cancer, according to Scott Gettinger, MD, professor of internal medicine (medical oncology) and disease aligned research team leader of the thoracic oncology program at Yale Cancer Center.
The CheckMate 017 and 057 trials originally established nivolumab (Opdivo, Bristol-Myers Squibb) as a standard salvage therapy for patients with advanced NSCLC. Previously, 5-year OS rates for advanced NSCLC were poor, at only 5% with conventional chemotherapy.
Both the CheckMate 017 and 057 trials compared 3 mg/kg nivolumab every 2 weeks compared with 75 mg/m2 docetaxel every 3 weeks among patients with stage IIIB/stage IV NSCLC and an ECOG performance status of 0 to 1. Treatment continued until disease progression or unacceptable toxicity.
CheckMate 017 included 272 patients with squamous NSCLC, and CheckMate 057 included 582 patients with nonsquamous NSCLC.
In the pooled analysis, researchers evaluated data from a total of 427 patients in each treatment group.
Researchers reported that 13.4% of patients achieved 5-year OS in the combined nivolumab groups compared with 2.6% of patients assigned docetaxel, representing a fivefold increase in OS.
“This is really unprecedented — we wouldn’t expect many patients to be out 5 years in this scenario,” Gettinger said during a press conference.
This benefit occurred among both the squamous and nonsquamous cohorts, he added.
Median OS was 11.1 months with nivolumab vs. 8.1 months with docetaxel (HR = 0.68; 95% CI, 0.59-0.78).
Researchers also observed a PFS benefit, with an 8% 5-year PFS rate in the nivolumab group compared with 0% in the docetaxel group (median PFS, 2.5 months vs. 3.5 months; HR = 0.79; 95% CI, 0.68-0.92).
“Again, we don’t see this at 5 years,” Gettinger said. “More commonly, we see zero patients without progression at 5 years, and that’s what we see with docetaxel.”
Median duration of response was 19.9 months (95% CI, 11.4-30.8) with nivolumab and 5.6 months (95% CI, 4.4-7) with docetaxel. At 5 years, 32.2% of responders remained in response with nivolumab.
Landmark PFS and OS analyses by PFS showed that of patients who were progression free at 2 years, 76% remained progression free at 3 years, 68% remained progression free at 4 years, and 60% remained progression free at 5 years, with 82% of these patients achieving 5-year OS.
Of patients who were progression free at 3 years, 90% were likely to remain without progression at 4 years, and 78% by 5 years, with 93% remaining alive at 5 years.
Of patients who achieved 4-year PFS, 88% were likely to achieve 5-year PFS and 100% were likely to remain alive at 5 years.
Researchers observed no new safety signals at the 5-year analysis, with only one additional grade 3 treatment-related adverse event of lipase elevation observed in the nivolumab group since the 3-year analysis. One patient discontinued nivolumab after 3 years due to treatment-related grade 2 eczema.
“These are the first randomized trials to report 5-year outcomes for a PD-1 axis inhibitor in patients with previously treated NSCLC,” Gettinger said. “There were no baseline clinical or tumor characteristics that clearly distinguished long-term survivors receiving nivolumab, and we looked at several of such variables.”
Notably, 10% of survivors at 5 years were off study drug after 8.8 months to 43.5 months of treatment and had not progressed or received subsequent therapy, he added.
“So, we clearly see benefit in our patients long after they finish a course of immunotherapy and need to stop for some reason,” he said. – by Alexandra Todak
Gettinger S, et al. Abstract OA14.04. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer; Sept. 7-10, 2019; Barcelona.
Disclosures: Gettinger reports consultant/advisory roles with Bristol-Myers Squibb and Nektar Therapeutics, and research funding to his institution from Ariad/Takeda, Bristol-Myers Squibb, Iovance Biotherapeutics and Genentech/Roche. Please see the abstract for all other authors’ relevant financial disclosures.