CHICAGO – Phase 3 results suggest ipilimumab plus nivolumab is no more effective than nivolumab alone in previously treated patients with metastatic squamous cell lung cancer and no matching biomarker.
However, there is evidence to suggest that patients with a high tumor mutational burden (TMB) and low programmed death–ligand 1 (PD-L1) tumor proportion score (TPS) may derive a benefit from the combination.
of the University of California, San Diego, and her colleagues presented results from this trial ( ) in a poster at the annual meeting of the American Society for Clinical Oncology. of Memorial Sloan Kettering Cancer Center in New York reviewed the data in a poster discussion session.
Patients and treatment
The researchers reported on 275 previously treated patients with stage IV or recurrent squamous cell lung cancer who were naive to checkpoint inhibitors. Patients were randomized to receive nivolumab (nivo) at 3 mg/m2 once every 2 weeks (n = 137) or the same dose of nivolumab plus ipilimumab (ipi + nivo) at 1 mg/m2 once every 6 weeks (n = 138).
The patients were stratified by gender and number of prior therapies (one vs. two or more), but they were not stratified by TMB or PD-L1 expression.
The PD-L1 TPS was unknown in 36% of patients, less than 5% in 57%, and 5% or greater in 43% of patients. TMB was unknown in 8% of patients, less than 10 mutations per megabase in 52%, and 10 mutations per megabase or greater in 48%.
Baseline characteristics were similar between the treatment arms. The median age was 67.5 years (range, 42-83 years) in the ipi + nivo arm and 68.1 years (range, 49-90 years) in the nivo arm. Most patients had received only one prior therapy – 85% and 83%, respectively – and most had a performance status of 1 – 71% and 72%, respectively.
There were no significant differences in outcomes between the treatment arms, and the study was closed early for futility.
The overall response rate was 18% in the ipi + nivo arm and 17% in the nivo arm, with one complete response occurring in each arm. The median duration of response was 9.1 months in the ipi + nivo arm and 8.6 months in the nivo arm.
The median progression-free survival was 3.8 months in the ipi + nivo arm and 2.9 months in the nivo arm (hazard ratio, 0.84; P = .19). The 24-month progression-free survival was 8.2% and 5.9%, respectively.
The median overall survival was 10.0 months in the ipi + nivo arm and 11.0 months in the nivo arm (HR, 0.97; P = .82). The 24-month overall survival was 27.6% and 20.1%, respectively.
There were no significant differences in outcomes by TMB or PD-L1 with the cutoffs used in this study, according to Dr. Bazhenova and colleagues, but different cutoffs are being explored.
The median progression-free survival was 4.4 months in TMB-high/PD-L1-low patients in the ipi + nivo arm, compared with 1.7 months in the TMB-high/PD-L1-low patients in the nivo arm. The median overall survival was 15.9 months and 10.3 months, respectively.
“It is slightly challenging to interpret the results without knowing the PD-L1 data of all patients in the cohort, and biomarker selection remains crucial for this combination,” Dr. Arbour said.