First-line immunotherapy for advanced NSCLC: A chink in nivolumab’s armour? Greater patient selection needed!

Late-breaking results from CheckMate-026

Stefan Zimmermann, ESMO 2016 Daily Reporter Associate Editor

Stefan Zimmermann, ESMO 2016 Daily Reporter Associate Editor

The clinical properties of the anti-programmed death-1 (PD-1) antibody nivolumab continue to be dissected in the expansive CheckMate trial programme across multiple cancer types, disease stages and lines of treatment. Nivolumab is approved in Europe and the USA in previously treated advanced non-small-cell lung cancer (NSCLC) having demonstrated a survival benefit versus docetaxel in CheckMate-017 and -057.1,2 Furthermore, patients with advanced NSCLC with PD-L1-positive tumours experienced durable responses with first-line nivolumab monotherapy in the phase I CheckMate-012 study.3 Yesterday Dr Mark Socinski of the UPMC Cancer Center, Pittsburgh, Philadelphia, USA, presented late-breaking results from CheckMate-026, one of the first studies in chemotherapy-naïve patients with stage IV or recurrent NSCLC to compare immunotherapy with a platinum-based regimen (Abstract LBA7_PR). A total of 541 patients received nivolumab 3 mg/kg every 2 weeks or investigator’s choice (IC) of platinum-based doublet chemotherapy every 3 weeks for up to 6 cycles. Despite an enriched population with PD-L1-positive tumours (threshold defined as ≥1%; n= 423), nivolumab did not show superior median progression-free survival compared with IC (4.2 months versus 5.9 months; hazard ratio 1.15, p=0.25).

While the threshold of PD-L1 positivity in CheckMate-026 was ≥1%, a similar study comparing first-line pembrolizumab with platinum-doublet chemotherapy in advanced NSCLC, KEYNOTE-024, used a much higher threshold of ≥50% (Abstract LBA8) and showed significant clinical benefit for the anti-PD-1 therapy. Let’s see whether the combination of nivolumab and ipilimumab, as in CheckMate-227, will trump chemotherapy in treatment-naïve, low PD-L1 expressors with NSCLC.

1. Brahmer J, et al. N Engl J Med 2015;373:123–35
2. Borghaei H, et al. N Engl J Med 2015;373:1627–39
3.Gettinger S, et al. J Clin Oncol 2016;34:2980–7
This article appeared in the Monday edition of the Daily Reporter