Ipilimumab plus pembrolizumab does not provide a survival benefit over pembrolizumab alone in patients with previously untreated, stage IV non-small cell lung cancer (NSCLC) and high PD-L1 expression, according to updated results of the KEYNOTE-598 study.1 

Ipilimumab did not improve progression-free survival (PFS) or overall survival (OS), according to Delvys Rodríguez-Abreu, MD, of Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria in Spain. 

Dr Rodríguez-Abreu presented these results at the 2022 European Lung Cancer Congress (ELCC).

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The phase 3 KEYNOTE-598 trial (ClinicalTrials.gov identifier: NCT03302234) enrolled 568 patients with stage IV NSCLC who had a PD-L1 tumor proportion score of 50% or higher and no targetable EGFR or ALK translocations.

The patients were randomly assigned 1:1 to receive pembrolizumab plus ipilimumab or pembrolizumab plus placebo. All patients received 200 mg of pembrolizumab every 3 weeks for up to 35 doses. Ipilimumab (1 mg/kg) or placebo was administered every 6 weeks for up to 18 doses.

In the primary analysis, ipilimumab did not improve efficacy and increased toxicity.2 As per a data monitoring committee recommendation, ipilimumab and placebo were discontinued, and pembrolizumab monotherapy was continued in both treatment arms.

In the current analysis, the median time from randomization to the data cutoff (October 1, 2021) was 33.6 months.1 The objective response rate was 46.5% in the ipilimumab arm and 46.1% in the placebo arm. The median duration of response was 22.1 months and 18.9 months, respectively.

There was no significant difference in OS (hazard ratio [HR], 1.05; 95% CI, 0.85-1.29) or PFS (HR, 0.99; 95% CI, 0.81-1.21) between the treatment arms. The 2-year PFS rate was 27.2% in the ipilimumab arm and 25.1% in the placebo arm. The 2-year OS rate was 48.0% and 48.5%, respectively.

“With continued follow-up, results do not demonstrate a survival benefit with pembrolizumab plus ipilimumab vs pembrolizumab alone,” Dr Rodriguez-Abreu said.

There was a higher incidence of adverse events (AEs) with ipilimumab. Grade 3-5 treatment-related AEs occurred in 35.1% of patients in the ipilimumab arm and 20.3% of those in the placebo arm. 

Immune-mediated AEs were also higher in the ipilimumab arm (44.3%) than in the placebo arm (32.0%). The overall safety profile continued to favor pembrolizumab alone with longer follow-up.

Disclosures: This research was supported by Merck Sharp & Dohme Corp. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


1. Rodríguez-Abreu D, Reck M, Şendur M, et al. Pembrolizumab plus ipilimumab or placebo in previously untreated metastatic NSCLC with PD-L1 tumor proportion score ≥50%: KEYNOTE-598 3-year follow-up. Presented at ELCC 2022; March 30 – April 2, 2022. Abstract 6MO.

2. Boyer M, Şendur M, Rodríguez-Abreu D, et al. 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. J Clin Oncol. 2021;39(21):2327-2338. doi:10.1200/JCO.20.03579