European Society for Medical Oncology Congress
European Society for Medical Oncology Congress
Perspective from Nicholas Rohs, MD
Perspective from Marina Garassino, MD
September 28, 2019
3 min read

Immunotherapy combination improves OS compared with chemotherapy in lung cancer subset

Perspective from Nicholas Rohs, MD
Perspective from Marina Garassino, MD
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BARCELONA, Spain — A combination of nivolumab and low-dose ipilimumab significantly improved OS compared with chemotherapy as first-line treatment for patients with advanced non-small cell lung cancer, according to results of the randomized phase 3 CheckMate 227 study presented at European Society for Medical Oncology Congress.

Researchers observed a survival benefit among patients with less than 1% PD-L1 expression, as well as those with expression of 1% or greater.

“The landscape of lung cancer has become very complex,” Solange Peters, MD, PhD, head of the thoracic malignancies program in the department of oncology at University of Lausanne in Switzerland, said during her presentation. “There are many options for front-line therapies these days. We would like to give front-line immunotherapy to as many patients as possible, very often combined with chemotherapy. In very specific patients, there is even a chemotherapy-sparing regimen. We really like if we can avoid chemotherapy in the front-line setting if possible.”

Previous results from CheckMate 227 showed nivolumab (Opdivo, Bristol-Myers Squibb), an anti-PD-1 antibody, in combination with ipilimumab (Yervoy, Bristol-Myers Squibb), an anti-CTLA-4 antibody, significantly extended PFS compared with chemotherapy alone for patients with advanced NSCLC with tumor mutational burden of at least 10 mutations per megabase.

Peters presented OS results from the final analysis of part 1 of the trial, which compared nivolumab-based regimens with chemotherapy for patients with stage IV or recurrent NSCLC and no known EGFR or ALK mutations.

In part 1, researchers randomly assigned 1,189 patients with PD-L1 expression of 1% or greater to one of three regimens: 3 mg/kg nivolumab every 2 weeks plus 1 mg/kg ipilimumab every 6 weeks (n = 396); 240 mg nivolumab every 2 weeks (n = 396); or histology-based chemotherapy (n = 397).

They also randomly assigned 550 patients with tumor PD-L1 expression of less than 1% to the nivolumab-plus-low-dose ipilimumab regimen (n = 187), 360 mg nivolumab every 3 weeks plus histology-based chemotherapy (n = 177) or chemotherapy alone (n = 186).

OS for nivolumab plus ipilimumab vs. chemotherapy among patients with tumor PD-L1 expression of at least 1% served as the primary endpoint.

Minimum follow-up for OS was 29.3 months.

Results showed patients with tumor PD-L1 expression of at least 1% achieved significantly longer median OS with the immunotherapy combination compared with chemotherapy (17.1 months vs. 14.9 months; HR = 0.79; 97.7% CI, 0.65-0.96). Patients in this subgroup who received nivolumab alone had median OS of 15.7 months (95% CI, 13.3-18.1).


PFS, objective response rate, and duration of response all appeared more favorable for patients treated with nivolumab plus ipilimumab compared with chemotherapy.

Researchers also observed longer median OS with nivolumab plus ipilimumab vs. chemotherapy among patients with PD-L1 expression of less than 1% (17.2 months vs. 12.2 months), as well as among all randomly assigned patients (17.1 months vs. 13.9 months).

Grade 3 or grade 4 treatment-related adverse events occurred among 33% of patients treated with nivolumab and ipilimumab, 19% of patients treated with nivolumab alone, and 36% of patients treated with chemotherapy.

The trial began before the approval of chemotherapy plus immunotherapy or immunotherapy alone for the front-line treatment of NSCLC, so the immunotherapy combination was not compared against the current standards of care. Researchers acknowledged this was the study’s primary limitation.

“This is interesting because it is the first phase 3 study proving this in the negative-based fashion of the combination of CTLA4 and anti-PD1 or anti-PDL1 in NSCLC,” Peters said. “The improvement was seen beyond the primary endpoint in unselected patients and to me represents a new front-line option.” – by John DeRosier



Peters S, et al. Abstract LBA4_PR; Presented at: European Society for Medical Oncology Congress; Sept. 27-Oct. 1, 2019; Barcelona, Spain.


Disclosures: Bristol-Myers Squibb funded this study. Peters reports consultant roles with AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Bioinvent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, and Merck Sharp & Dohme. Please see the abstract for all other authors' relevant financial disclosures.