In the first-line treatment of metastatic NSCLC, adding ipilimumab to pembrolizumab does not significantly improve efficacy and yields greater toxicity compared to pembrolizumab monotherapy with programmed death ligand 1 (PD-L1) expression tumor proportion score ≥ 50% and no targetable EGFR or ALK aberration, according to study findings in Journal of Clinical Oncology. 

Pembrolizumab-ipilimumab should not be used in place of pembrolizumab monotherapy in this population, according to study researcher Michael Boyer, MBBS, PhD, of Chris O’Brien Lifehouse in New South Wales, Australia and colleagues. 

The randomized, double blind, placebo-controlled phase 3 study took place at 171 sites in 24 countries.  

Patients 18 years or older with confirmed stage IV NSCLC, PD-L1 TPS ≥ 50%, no previous systematic therapy for metastatic NSCLC, an Eastern Cooperative Oncology Group performance status score of 0 or 1 and ≥ 1 lesion measurable per RECIST v1.1 were eligible for the enrollment. 

568 patients were randomized 1:1 to ipilimumab 1 mg/kg (N = 284) or placebo (N = 284) every 6 weeks for up to 18 doses.  

All patients included in the study received pembrolizumab 200 mg every 3 weeks for up to 35 doses.  

The primary endpoints were overall survival and progression free survival. 

According to the study, median OS was 21.4 months for pembrolizumab-ipilimumab vs 21.9 months for pembrolizumab-placebo (HR = 1.08; 95% CI, 0.85 to 1.37; P = .74). 

Median PFS was 8.2 months for pembrolizumab-ipilimumab vs 8.4 months for pembrolizumab-placebo (HR, 1.06; 95% CI, 0.86 to 1.30; P = .72).  

Grade 3-5 adverse events occurred in 62.4% of patients who received pembrolizumab-ipilimumab, compared to 50.2% in the pembrolizumab-placebo group. 

Adverse events led to death in 13.1% of those who received pembrolizumab-ipilimumab and 7.5% of those in the pembrolizumab-placebo cohort.  

The study ended at the recommendation of the external data and safety monitoring committee due to futility. 

“PD-L1 expression on tumor and/or immune cells helps identify patients with NSCLC who experience better outcomes with this treatment class,” Boyer and colleagues wrote. “For patients with the highest PD-L1 expression levels, defined as a tumor proportion score ≥ 50%, pembrolizumab monotherapy is a widely approved and accepted standard of care based on results of KEYNOTE-024, in which pembrolizumab significantly improved overall survival, progression-free survival, and objective response rate vs platinum-doublet chemotherapy. Despite the effectiveness of pembrolizumab monotherapy in this population, which was confirmed in KEYNOTE-042, almost 50% of patients die within 2 years and more effective therapies are needed.” 


By Dave Quaile