Pembrolizumab Plus Ipilimumab or Placebo for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50%: Randomized, Double-Blind Phase III KEYNOTE-598 Study.

Abstract

PURPOSE:

Pembrolizumab monotherapy is standard first-line therapy for metastatic non-small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 50% without actionable driver mutations. It is not known whether adding ipilimumab to pembrolizumab improves efficacy over pembrolizumab alone in this population.

METHODS:

In the randomized, double-blind, phase III KEYNOTE-598 trial (ClinicalTrials.gov identifier: NCT03302234), eligible patients with previously untreated metastatic NSCLC with PD-L1 TPS ≥ 50% and no sensitizing EGFR or ALK aberrations were randomly allocated 1:1 to ipilimumab 1 mg/kg or placebo every 6 weeks for up to 18 doses; all participants received pembrolizumab 200 mg every 3 weeks for up to 35 doses. Primary end points were overall survival and progression-free survival.

RESULTS:

Of the 568 participants, 284 were randomly allocated to each group. Median overall survival was 21.4 months for pembrolizumab-ipilimumab versus 21.9 months for pembrolizumab-placebo (hazard ratio, 1.08; 95% CI, 0.85 to 1.37; P = .74). Median progression-free survival was 8.2 months for pembrolizumab-ipilimumab versus 8.4 months for pembrolizumab-placebo (hazard ratio, 1.06; 95% CI, 0.86 to 1.30; P = .72). Grade 3-5 adverse events occurred in 62.4% of pembrolizumab-ipilimumab recipients versus 50.2% of pembrolizumab-placebo recipients and led to death in 13.1% versus 7.5%. The external data and safety monitoring committee recommended that the study be stopped for futility and that participants discontinue ipilimumab and placebo.

CONCLUSION:

Adding ipilimumab to pembrolizumab does not improve efficacy and is associated with greater toxicity than pembrolizumab monotherapy as first-line treatment for metastatic NSCLC with PD-L1 TPS ≥ 50% and no targetable EGFR or ALK aberrations. These data do not support use of pembrolizumab-ipilimumab in place of pembrolizumab monotherapy in this population.

• Authors: Michael Boyer, Mehmet A N Şendur, Delvys Rodríguez-Abreu, Keunchil Park, Dae Ho Lee, Irfan Çiçin, Perran Fulden Yumuk, Francisco J Orlandi, Ticiana A Leal, Olivier Molinier, Nopadol Soparattanapaisarn, Adrian Langleben, Raffaele Califano, Balazs Medgyasszay, Te-Chun Hsia, Gregory A Otterson, Lu Xu, Bilal Piperdi, Ayman Samkari, Martin Reck, KEYNOTE-598 Investigators
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 39 Issue 21 Pg. 2327-2338 (07 20 2021) ISSN: 1527-7755 [Electronic] United States
• PMID: 33513313 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• B7-H1 Antigen
• CD274 protein, human
• Ipilimumab
• pembrolizumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (pharmacology, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• B7-H1 Antigen (drug effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Double-Blind Method
• Female
• Humans
• Ipilimumab (pharmacology, therapeutic use)
• Lung Neoplasms (drug therapy)
• Male
• Middle Aged