The following article features coverage from the European Society for Medical Oncology (ESMO) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

First-line nivolumab plus low-dose ipilimumab improved overall survival (OS) compared with chemotherapy among patients with advanced non-small cell lung cancer (NSCLC), according to findings from a final analysis of part 1 of the phase 3 CheckMate-227 trial ( Identifier: NCT02477826). The findings were presented at the 2019 European Society of Medical Oncology (ESMO) meeting in Barcelona, Spain.1 

The findings suggest the 2-agent combination immunotherapy regimen is a viable chemotherapy-free frontline treatment strategy. 

Related Articles

“In my opinion, these data are practice changing,” said lead study author Solange Peters, PhD, of the Centre Hospitalier Universitaire Vaudois, in Lausanne, Switzerland, in a press release.2 “We already had several frontline treatment options for these patients, including chemotherapy compared with an anti–PD-1 agent or an anti–PDL-1 agent alone. And now we have a chemotherapy-sparing option of nivolumab plus ipilimumab.”

Continue Reading

However, it is not yet clear which regimen will offer patients the best long-term prognosis, Dr Peters cautioned. 

“The 5-year survival from trials with these treatments will teach us if any of the options are better than the others,” she said. “The second critical point will be to compare toxicities.”

The 2 agents are immune checkpoint inhibiting antibodies with complementary molecular mechanisms of action that can unleash antitumor immunity; nivolumab targets programmed cell death protein 1 (PD-1) and ipilimumab targets anticytotoxic T lymphocyte antigen 4 (CTLA-4). CheckMate-227 was initiated prior to approval of chemotherapy plus immunotherapy regimens or immune checkpoint inhibition monotherapy, meaning that outcomes for nivolumab plus low-dose ipilimumab were not compared with what have become the standards of care. An exploratory analysis suggested the combination was more effective than nivolumab monotherapy among patients with PD-L1–positive NSCLC.

The low dose of ipilimumab (1 mg every 6 weeks) rendered the regimen tolerable, with a low rate of treatment-related discontinuations, Peters noted.

Part 1 of the Checkmate-227 study enrolled 1189 patients with previously untreated stage IV or recurrent NSCLC with at least 1% PD-L1 expression. Patients were randomly assigned to receive nivolumab plus low-dose ipilimumab, nivolumab, or histology-based chemotherapy. Another 550 patients with less than 1% PD-L1 expression were randomly assigned to receive nivolumab plus low-dose ipilimumab, nivolumab plus chemotherapy, or chemotherapy only. 

OS was significantly prolonged among patients receiving nivolumab plus ipilimumab across PD-L1 expression categories (median OS [PD-L1>1%], 17.1 months; 95% CI, 15.0-20.1 months) compared with those receiving chemotherapy (14.9 months; 95% CI, 12.7-16.7 months; hazard ratio [HR], 0.79; P =.007). 

Progression-free survival (PFS), objective response rate, and duration of response for nivolumab plus ipilimumab were also superior to chemotherapy, Dr Peters reported.

Incidence of grade 3/4 treatment-related adverse events (TRAEs) was 33% for the nivolumab plus low-dose ipilimumab group, 19% for nivolumab monotherapy, and 36% for patients receiving chemotherapy. 

Read more of Cancer Therapy Advisor‘s coverage of the ESMO annual meeting by visiting the conference page.


  1. 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. Presented at: ESMO Congress 2019; Madrid, Spain: September 8-12, 2017. Abstract LBA4_PR.
  2. European Society of Medical Oncology (ESMO). Two immunotherapy drug combination offers chemotherapy-free option for advanced NSCLC [press release]. Accessed September 28, 2019.