Five-fold increase of OS at 5 years with nivolumab vs docetaxel

Pooled data of the CheckMate 017 and CheckMate 057 studies showed that non-small-cell lung cancer (NSCLC) patients who were treated with the immune checkpoint inhibitor nivolumab in the second-line setting after chemotherapy failure had a 5-fold increase in 5-year overall survival (OS) when compared with docetaxel. Moreover, nivolumab was well tolerated on long-term treatment and no new safety signals occurred.

CheckMate 017 and CheckMate 057 included a total of 854 patients with advanced NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1, and progression during or after first-line platinum-based chemotherapy. They were randomised to nivolumab (n=427) or docetaxel (n=427) until progression or unacceptable toxicity. OS was the primary endpoint for both studies [1].

At the follow-up at 5 years, 50 patients who were treated with nivolumab and 9 patients who received docetaxel, were still alive. In general, baseline characteristics of those patients in both arms were similar to the overall population and patients who survived less than one year. Of survivors, a higher percentage of patients on nivolumab had ECOG performance status 0 or PD-L1 expression >1%; and on docetaxel a higher percentage had ECOG performance status 0 and stage IIIB NSCLC. It was demonstrated that the 5-year OS for patients on nivolumab was 13.4% compared to 2.6% for patients being treated with docetaxel. Mean OS was 11.1 months for nivolumab and 8.1 for docetaxel (HR 0.58; 95% CI 0.59-0.78; see Figure). The OS benefit of nivolumab was seen in all subgroups and irrespective of PD-L1 expression. Progression-free survival (PFS) at 5 years was 8.0% on nivolumab and 0% on docetaxel.

Although it is still challenging to predict long-term response with the current lack of reliable biomarkers it was found that patients who had no disease progression after 2 and 3 years of treatment with nivolumab had a reasonable high chance to remain progression-free at 5 years (60% and 78% chance, respectively). With regard to safety, no new safety signals were observed during the longer follow-up. Between the 3- and 5-years follow-up, 26% of nivolumab-treated patients reported a treatment-related adverse event (AE) of any grade, of which only 3% turned out to be a grade 3-4 AE. The most AEs with a potential immunological cause were related to skin (13% of patients; no grade 3 or 4). There was 1 patient who discontinued nivolumab after 3 years as a result of treatment-related grade 2 eczema.

Prof. Scott Gettinger (Yale Cancer Center, USA) emphasised the importance of these long-term results by concluding that these data are the first to come out of randomised trials reporting 5-year outcomes for a single-agent PD-1 axis inhibitor in patients with previously treated NSCLC. Also, he said that 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. “This clearly shows the benefit of this treatment regimen long after patients finish a course of immunotherapy and need to stop for some reason.”

1. Gettinger S, et al. OA14.04. WCLC 2019.

Posted on 8 November 201918 March 2021