{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:21:32Z","timestamp":1792027292121,"version":"4.4.0"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bristol Myers Squibb","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}]},{"name":"National Institutes of Health\/National Cancer Institute Cancer Center","award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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 \u2264 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\u201358.5 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.<\/jats:p>","DOI":"10.3390\/cancers14092300","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T13:10:26Z","timestamp":1651756226000},"page":"2300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Proton Pump Inhibitor Use and Efficacy of Nivolumab and Ipilimumab in Advanced Melanoma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0912-6198","authenticated-orcid":false,"given":"Krisztian","family":"Homicsko","sequence":"first","affiliation":[{"name":"Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2279-6906","authenticated-orcid":false,"given":"Reinhard","family":"Dummer","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Universit\u00e4ts Spital, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Hoeller","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jedd D.","family":"Wolchok","sequence":"additional","affiliation":[{"name":"Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"},{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY 10021, USA"},{"name":"Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Stephen","family":"Hodi","sequence":"additional","affiliation":[{"name":"Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Larkin","sequence":"additional","affiliation":[{"name":"Medical Oncology, Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8322-475X","authenticated-orcid":false,"given":"Paolo A.","family":"Ascierto","sequence":"additional","affiliation":[{"name":"Melanoma Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori IRCCS Fondazione Pascale, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Division of Cancer Services, Princess Alexandra Hospital, Woolloongabba, QLD 4102, Australia"},{"name":"Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Greenslopes, QLD 4120, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Robert","sequence":"additional","affiliation":[{"name":"Dermatology Service, Gustave Roussy, 94805 Villejuif, France"},{"name":"Melanoma Research Unit, Paris-Saclay University, 91400 Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Postow","sequence":"additional","affiliation":[{"name":"Department of Medicine, Weill Cornell Medical College, New York, NY 10021, USA"},{"name":"Melanoma Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Re","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, NJ 08543, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Paulucci","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, NJ 08543, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darin","family":"Dobler","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, NJ 08543, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Michielin","sequence":"additional","affiliation":[{"name":"Precision Oncology Center, Centre Hospitalier Universitaire Vaudois (CHUV), 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e000948","DOI":"10.1136\/jitc-2020-000948","article-title":"Evolving impact of long-term survival results on metastatic melanoma treatment","volume":"8","author":"Michielin","year":"2020","journal-title":"J. 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