CheckMate 227 Further Supports First-Line Nivolumab–Ipilimumab For Advanced NSCLC

Author:  By Lynda Williams, Senior medwireNews Reporter

medwireNews: Findings from the CheckMate 227 trial show better overall survival (OS) with nivolumab plus ipilimumab than platinum doublet chemotherapy for patients with treatment-naïve advanced non-small-cell lung cancer (NSCLC) and PD-L1 tumour expression above 1%. 

The phase III study results were reported at the ESMO 2019 Congress in Barcelona, Spain, by Solange Peters, from Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, and simultaneously published in The New England Journal of Medicine. 

Median OS was 17.1 months for the 396 patients with a PD-L1 of at least 1% who were randomly assigned to receive nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks, compared with 14.9 months for the 397 patients who instead received up to four cycles of platinum-based chemotherapy at 3-week intervals. 

Although the proportional hazards assumption was not met, the difference in OS was significantly different, with a hazard ratio of 0.79, which the researchers say “provides an overall estimate of benefit” that “should be interpreted in the context of the shape of the curves, which are characterized by transient initial survival benefit with chemotherapy, followed by long-term benefit with nivolumab plus ipilimumab”. 

Two-year OS was achieved by 40.0% and 32.8% of the nivolumab–ipilimumab and chemotherapy arms, respectively, with corresponding median durations of response of 23.2 and 6.2 months. 

Furthermore, a significant OS benefit was also observed with the combination treatment for the 187 patients with a tumour PD-L1 level below 1%, with a median duration of 17.2 months versus 12.2 months for the 186 patients given chemotherapy. And this translated into an improved OS with nivolumab–ipilimumab in the combined population of patients regardless of PD-L1 expression, at 17.1 months versus 13.9 months with chemotherapy. 

The researchers also cite higher rates of complete response and a longer duration of response with nivolumab plus ipilimumab when compared with a third treatment arm of nivolumab monotherapy. “Although this trial was not powered to compare the two regimens, our findings show better efficacy with nivolumab plus ipilimumab than with nivolumab monotherapy within the same trial”, they comment.  

Finally, Matthew Hellman et al report that “[n]o new safety concerns emerged with longer follow-up”, with comparable rates of grade 3–4 treatment-related adverse events in the combination and chemotherapy arms (32.8 vs 36.0%).  

However, the combination arm was associated with more serious adverse events of any grade (24.5 vs 13.9%) and a greater rate of events leading to treatment discontinuation (18.1 vs 9.1%), the researchers note. 

References  

Peters S, Ramalingam SS, Paz-Ares L, et al. Nivolumab (NIVO) + low-dose ipilimumab (IPI) vs platinum-doublet chemotherapy (chemo) as first-line (1L) treatment (tx) for advanced non-small cell lung cancer (NSCLC): CheckMate 227 part 1 final analysis. ESMO 2019 Congress, Barcelona, Spain: 27 September – 1 October. LBA4_PR

Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med 2019; 28 September 2019. DOI: 10.1056/NEJMoa1910231