Proton Pump Inhibitor Use and Efficacy of Nivolumab and Ipilimumab in Advanced Melanoma

Krisztian Homicsko, Reinhard Dummer, Christoph Hoeller, Jedd D. Wolchok, F. Stephen Hodi, James Larkin, Paolo A. Ascierto, Victoria Atkinson, Caroline Robert, Michael A. Postow, Sandra Re, David Paulucci, Darin Dobler, Olivier Michielin

    Research output: Contribution to journalArticlepeer-review

    9 Citations (Scopus)

    Abstract

    The impact of proton pump inhibitors (PPIs) on clinical outcomes with first-line immune checkpoint inhibitors (ICIs) in patients with metastatic melanoma was previously analyzed in the phase II study, CheckMate 069. This retrospective analysis utilized data from three phase II/III studies of first-line ICI therapy in untreated advanced melanoma: CheckMate 066, 067, and 069. All randomized patients with PPI use ≤ 30 days before initiating study treatment were included in the PPI-use subgroup. Possible associations between baseline PPI use and efficacy were evaluated within each treatment arm of each study using multivariable modeling. Approximately 20% of 1505 randomized patients across the studies reported baseline PPI use. The median follow-up was 52.6–58.5 months. Objective response rate (ORR), progression-free survival (PFS), and overall survival analyses provided insufficient evidence of a meaningful association between PPI use and efficacy outcomes with nivolumab-plus-ipilimumab, nivolumab, or ipilimumab therapy. In five of the six ICI treatment arms, 95% confidence intervals for odds ratios or hazard ratios traversed 1. Significant associations were observed in the CheckMate 069 combination arm between PPI use and poorer ORR and PFS. This multivariable analysis found insufficient evidence to support meaningful associations between PPI use and ICI efficacy in patients with advanced melanoma.

    Original languageEnglish
    Article number2300
    JournalCancers
    Volume14
    Issue number9
    DOIs
    Publication statusPublished - 1 May 2022

    Keywords

    • checkpoint inhibitors
    • melanoma
    • pooled analysis
    • proton pump inhibitors

    Cite this