Nivolumab response a positive indicator for long-term survival in NSCLC
Patients with previously-treated non-small-cell lung cancer (NSCLC) who responded early to nivolumab at 6 months showed better long-term survival compared with responders to docetaxel, according to pooled analyses of CheckMate 017 and CheckMate 057 presented at the AACR 2019 Annual Meeting.
At 4 years, the overall survival (OS) rate for all patients who received nivolumab was 14 percent, a rate almost threefold higher than those treated with docetaxel (5 percent). [AACR 2019, abstract CT195]
When the analyses were restricted to a subgroup of patients with partial response (PR) or complete response (CR) at 6 months, the survival benefit of nivolumab was even more pronounced over docetaxel (4-year OS rate, 58 percent vs 12 percent).
“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,” said study co-investigator Dr Scott Antonia, director of the Duke Cancer Institute Center for Cancer Immunotherapy in Durham, North Carolina, US in a press release.
“These long-term survival outcomes are particularly interesting given that, historically, the average 5-year survival rate for this patient population is approximately 5 percent,” he continued.
The CheckMate 017 and CheckMate 057 are two phase III studies which randomized a total of 854 patients (median age ~62.5 years) with previously-treated advanced NSCLC in a 1:1 ratio to receive nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks).
Analyses stratified by response status revealed that responders to nivolumab (CR/PR) at 6 months consistently had better OS vs patients with similar response status to docetaxel across year 1 (81 percent vs 62 percent), year 2 (63 percent vs 38 percent), year 3 (61 percent vs 26 percent), and year 4 (58 percent vs 12 percent).
Among patients with stable disease, the nivolumab arm also showed higher OS rates through to year 4 compared with the docetaxel arm (19 percent vs 2 percent).
Furthermore, patients in the nivolumab arm had a longer response duration than those in the docetaxel arm (median, 24 vs 6 months).
There were no new safety signals during the long-term follow-up. Treatment-related adverse events (TRAEs) leading to discontinuation occurred in 8.7 percent of patients in the nivolumab arm, with skin reactions being the most commonly reported for immune-related TRAE (incidence rate, 38.6/100 person-years).
The results demonstrate that response to nivolumab confers a durable survival benefit over docetaxel even after disease progression, according to the researchers.
Consistent with the global CheckMate 017 and 057 studies, the phase III CheckMate 078 which enrolled a predominantly Chinese population (n=504, median age 60 years) also showed that OS was significantly longer with nivolumab than with docetaxel (median, 12.0 vs 9.6 months, hazard ratio, 0.68; p=0.0006) over a median follow-up of 10.4 months. [J Thorac Oncol 2019;14:867-875]