The combination of nivolumab plus low-dose ipilimumab led to a longer duration of overall survival (OS) versus chemotherapy in patients with advanced non-small cell lung cancer (NSCLC), independent of  PD-L1 expression level, according to a secondary analysis of the CheckMate 227 trial.

In the phase III trial  presented at the European Society of Medical Oncology (ESMO) Congress 2019 in Barcelona by Professor Solange Peters, MD, from the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, patients with a PD-L1 expression level of ≥1%, the median OS duration was 17.1 months (95% CI 15.0-20.1) with nivolumab plus ipilimumab compared to 14.9 months (95% CI 12.7-16.7) with chemotherapy (P=0.007).

Patients with a PD-L1 expression level <1% also had OS benefits, with a median duration of 17.2 months (95% CI 12.8-22.0) with the immunotherapy combination compared to 12.2 months (95% CI 9.2-14.3) with chemotherapy.

Two-year OS rates were 40% with the immunotherapy combination and 32.8% with chemotherapy, found the study which was also published in the New England Journal of Medicine.

In terms of treatment related events, 32.8% of patients who received the immunotherapy combination experienced grade 3 or 4 treatment-related adverse events compared to 36% of patients who had chemotherapy.

Prof. Peters noted that one limitation of the trial was that it did not compare the immunotherapy combination treatment with the current standard of care because it commenced before chemotherapy/immunotherapy or immunotherapy alone was approved for the front-line treatment of NSCLC.

“Unfortunately, we did not include a treatment arm with the combination of chemotherapy plus nivolumab in the PD-L1 positive cohort, but only in the negative one,” she said.

She said the next step was to develop an algorithm to select the best front-line treatment for each patient.

“We need to wait for a little more time to see which treatment really gives rise to improved long-term survival. The five-year survival from trials with these treatments will teach us if any of the options are better than others,” she said.

Commenting on the trial results, Dr Marina Chiara Garassino, Istituto Nazionale dei Tumori, Milan, Italy, said, “These data show we have a new treatment option for the first-line treatment of metastatic NSCLC, to add to the current treatment options of chemotherapy plus immunotherapy regardless of PD-L1 level or immunotherapy as single agent for patients with PD-L1 scores of at least 50%.”

But she cautioned, “We don’t yet know if the findings are practice changing. We need to understand which treatment is best for each patient: chemotherapy plus immunotherapy, immunotherapy alone or immunotherapy plus immunotherapy.”

The phase III CheckMate-227 trial randomised treatment naive patients with metastatic NSCLC according to PD-L1 expression. Patients (n=1189) with ≥1% PD-L1 expression were randomised in a 1:1:1 ratio to  NIVO plus low dose IPI (n=396), chemo alone (n=397), or NIVO plus chemo (n=396).

Patients with PD-L1 expression <1% (n=550) were randomised to NIVO plus low-dose IPI (n=187), chemo alone (n=186) or NIVO plus chemo (n=177).

Patients were treated until disease progression, unacceptable toxicity or for two years. Primary endpoints were PFS in high TMB populations and OS in PD-L1 ≥ 1% populations.

CheckMate-337 was funded by Bristol-Myers Squibb (BMS) and Ono Pharmaceutical.