Prof. Michael Boyer of the Chris O’Brien Lifehouse and the University of Sydney discusses 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.
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Pembrolizumab monotherapy is a normal first-line treatment with a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of about 50 percent without actionable driver mutations for metastatic non-small-cell lung cancer (NSCLC). It is not clear if the addition of ipilimumab to pembrolizumab in this population increases efficacy compared to pembrolizumab alone.
In the randomized, double-blind, phase III KEYNOTE-598 trial (ClinicalTrials.gov identifier: NCT03302234), qualified patients with previously untreated metastatic NSCLC were randomly allocated 1:1 to ipilimumab 1 mg/kg or placebo every 6 weeks for up to 18 doses with PD-L1 TPS ⁇ 50% and no sensitizing EGFR or ALK aberrations; all participants received pembrolizumab 200 mg every 3 weeks for up to 18 doses. General survival and progression-free survival were the key endpoints.
Of the 568 participants, 284 were assigned to each group at random. The median overall survival for pembrolizumab-ipilimumab was 21.4 months, compared with 21.9 months for pembrolizumab-placebo (hazard ratio, 1.08; 95% CI, 0.85 to 1.37; P = .74). Pembrolizumab-ipilimumab median progression-free survival was 8.2 months versus 8.4 months for pembrolizumab-placebo (hazard ratio, 1.06; 95 percent CI, 0.86 to 1.30; P = .72). In 62.4 percent of pembrolizumab-ipilimumab recipients versus 50.2 percent of pembrolizumab-placebo recipients, Grade 3-5 adverse effects occurred and 13.1 percent versus 7.5 percent contributed to the death. The external data and safety control committee recommended that the research be halted for futility and that ipilimumab and placebo be discontinued by the participants.
Adding ipilimumab to pembrolizumab does not boost efficacy and is associated with greater toxicity than first-line treatment with pembrolizumab monotherapy for metastatic NSCLC with PD-L1 TPS ⁇ 50% and no targetable aberrations of EGFR or ALK. These data do not support the use of pembrolizumab-ipilimumab in this population in place of monotherapy with pembrolizumab.