Dr Khalil on the Use of Nivolumab/Ipilimumab Combination in NSCLC

Maya Khalil, MD, assistant professor of medicine, Division of Hematology and Oncology, the University of Alabama at Birmingham (UAB), oncologist, O’Neal Comprehensive Cancer Center, UAB Medicine, discusses key clinical trial updates on the use of nivolumab (Opdivo) and ipilimumab (Yervoy) with or without chemotherapy in non–small cell lung cancer (NSCLC).

Updated analyses from the phase 3 CheckMate 227 (NCT02477826) and CheckMate 9LA(NCT03215706) trials have aided in clarifying and identifying patient subgroups that have the potential to benefit from the use of nivolumab (Opdivo) and ipilimumab (Yervoy) either with or without chemotherapy.

The phase 3 CheckMate 227 trial evaluated the use of nivolumab and ipilimumab vs platinum-based chemotherapy in patients with stage IV or recurrent NSCLC without prior exposure to systemic therapy, Khalil begins. Patients with PD-L1 positivity were randomly assigned to recieve nivolumab and ipilimumab vs chemotherapy, while those in the PD-L1-negative group received nivolumab and ipilimumab vs nivolumab alone or chemotherapy. 

The experimental regimen provided a clear overall survival benefit to patients in both groups compared with chemotherapy, Khalil states. Similarly, progression-free survival (PFS) and duration of response (DOR) were both improved in the PD-L1–positive group with nivolumab and ipilimumab, she says. Additionally, the 5-year median OS in the PD-L1–negative group was 17.4 months. The subgroup analysis of the trial demonstrated that the experimental regimen was not favored in patients with liver metastasis and no smoking history, Khalil adds.

The combination of nivolumab and ipilimumab was also evaluated in combination with 2 cycles of platinum chemotherapy in the phase 3 CheckMate 9LA trial, Khalil continues. Patients in this same population were randomized to the experimental regimen vs 4 cycles of chemotherapy alone, and were treated until disease progression, unacceptable toxicity, or the completion of 2 years of immunotherapy. In this trial, the experimental regimen improved 3-year overall survival rate vs chemotherapy alone regardless of PD-L1 status, Khalil reports.

Additional mutation analysis revealed that patients with STK11, KRAS, and KEAP1 mutations experienced the most benefit from nivolumab and ipilimumab plus chemotherapy, Khalil notes. As patients with these mutations often develop resistance to immunotherapy, the use of CTLA-4 and PD-L1 inhibitor combinations with or without chemotherapy should be considered.

Editor's Note: Dr. Khalil reports serving as a principal investigator on trials in collaboration with/sponsored by: National Cancer Institute, Bristol Myers Squibb, Amgen, Top Alliance, Janssen, Cantargia, Guardant Health, Numab, Nitto BioPharma, Spectrum Pharmaceuticals, Eastern Cooperative Oncology Group (ECOG), Southwest Oncology Group (SWOG), Alliance cooperative group.