Five-year results of a phase I trial showed durable responses and long-term overall survival (OS) in a proportion of patients with pretreated advanced non–small-cell lung cancer (NSCLC) who received the PD-1 inhibitor nivolumab.
Two randomized phase III studies have found that advanced NSCLC patients fared better with nivolumab than with docetaxel, leading to the agent’s approval in this setting. “However, there is limited information about long-term efficacy and safety of such therapies in patients with NSCLC, including a lack of published data on outcomes at 5 years, a clinical landmark in oncology,” wrote study authors led by Scott Gettinger, MD, of the Yale Cancer Center in New Haven, Connecticut.
The phase I CA209-003 trial was an early study of nivolumab, including 306 patients with a variety of solid tumors; of those, 129 patients had previously treated advanced NSCLC. The new analysis extended the follow-up out to a minimum of 58.25 months; the results were published in the Journal of Clinical Oncology.
At baseline, the median age of patients was 65 years, and 61.2% of patients were men. Of the 68 patients with quantifiable tumor PD-L1 expression, 55.9% had ≥ 1% expression and 19.1% had ≥ 50% expression.
The median OS in the full cohort was 9.9 months, and the estimated 5-year OS rate was 16%. That rate varied slightly based on the nivolumab dose received; those who received 1 mg/kg had a 5-year OS rate of 13%, compared with 26% in those receiving 3 mg/kg and 11% in those receiving 10 mg/kg. Those with PD-L1 expression of < 1% had a 5-year OS rate of 20%, compared with 23% in those with ≥ 1% expression; the rate in those with ≥ 50% expression was 43%.
Most of the 5-year survivors (87.5%) were current or former smokers. Two of eight evaluable survivors had EGFR mutations. Generally, the characteristics of survivors were similar to the rest of the cohort, the authors noted. Of the survivors, 75.0% achieved a partial response to nivolumab, while 12.5% had stable disease, and 12.5% had progressive disease as their best response during therapy. Among the 22 responders to nivolumab, 12 had an OS duration of at least 5 years.
Most of the 5-year survivors (75%) received no further therapy after nivolumab, and they had no evidence of progressive disease at the last follow-up for data cutoff.
“The results from this analysis of CA209-003 demonstrate that nivolumab treatment can enable long-term survival in a diverse population of patients with previously treated advanced NSCLC,” the authors concluded. “Considering the historically low 5-year survival rate for patients with metastatic lung cancer, the estimated 5-year OS rate…constitutes a milestone in the advancement of lung cancer treatment.”