Across the two studies – CheckMate 017 and 057 – 854 patients were randomized 1:1 following progression on platinum therapy to either nivolumab at 3 mg/kg once every 2 weeks or docetaxel at 75 mg/m2 once every 3 weeks until further progression or unacceptable toxicity. Previously reported overall survival (OS) outcomes favored nivolumab.
At a minimum follow-up of 5.4 years, 50 nivolumab-treated patients and 9 docetaxel-treated patients were still alive.
The 5-year OS rates were 13.4% in the nivolumab arm and 2.6% in the docetaxel arm. The 5-year progression-free survival (PFS) rates were 8% and 0%, respectively.
There were no new safety signals with nivolumab, and there was no evidence of select late-onset grade 3-4 adverse events.
According to the study authors, this analysis is the longest phase 3 follow-up to date of a PD-1 inhibitor in previously treated, advanced NSCLC, and it suggests that “long-term survival beyond 5 years may ... be possible in NSCLC.”
“The results indicate that some patients with NSCLC can have long-lasting benefit from checkpoint inhibitors. We have seen similar results in terms of long-term OS with pembrolizumab,” said investigator Hossein Borghaei, DO, chief of thoracic medical oncology at the Fox Chase Cancer Center in Philadelphia.
Dr. Borghaei said the question now is “how to identify the population that really benefits from these treatments. We think PD-L1–high [patients] have a better chance, [as do patients with] tumors that have a higher percentage of tumor-infiltrating lymphocytes, but there’s nothing concrete beyond that.”
No baseline clinical or tumor factors emerged to distinguish between long-and short-term survivors, but the 5-year OS rate was 18.3% among nivolumab-treated patients with PD-L1 expression at or above 1% versus 8% among patients with expression below 1%.
The optimal duration of nivolumab treatment beyond 1 year is also uncertain.
The median duration of therapy was 36.9 months in the 5-year survivors treated with nivolumab, and 36% of patients (18/50) were still on nivolumab at the 5-year mark.
The median duration of time off treatment was 41.9 months among patients who discontinued nivolumab. Five patients (10%) were off treatment with no subsequent therapy and had not progressed at 5 years, “suggesting benefit even for patients who stopped nivolumab treatment,” the researchers wrote.
They also found that nivolumab-treated patients who remained alive at 3 years appeared to stabilize and plateau thereafter, with early response suggesting better long-term outcomes. The majority of patients without disease progression at 2, 3, and 4 years, for instance, remained progression free at 5 years. Nearly one-third of patients who achieved an objective response with nivolumab – but none of the patients who responded to docetaxel – had ongoing responses at 5 years.
Similarly, nivolumab-treated patients without disease progression at 2 years and 3 years had an 82% and 93% chance of survival, respectively, and a 59.6% and 78.3% chance of remaining progression free at 5 years.
This research was funded by Bristol-Myers Squibb. Dr. Borghaei and coauthors disclosed numerous ties to the company, including employment.