Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Sep 1;5(9):1631-1641.
doi: 10.1158/2767-9764.CRC-25-0033.

Modulating Treatment Outcomes of Patients with Solid Tumors in Immunotherapy Trials: A Drug Interaction Analysis from a Phase I Unit

Camila Braganca Xavier  1 , Clark R Andersen  2 , JoAnn Lim  1 , Julian H Slade  1 , Stacie A Bean  1 , Lei Kang  1 , Hung Le  1 , Apostolia M Tsimberidou  1 , Aung Naing  1 , David S Hong  1 , Ecaterina E Dumbrava  1 , Jordi Rodon Ahnert  1 , Paula R Pohlmann  1 , Sarina A Piha-Paul  1 , Stephane Champiat  1 , Timothy A Yap  1 , Tin-Yun Tang  1 , Funda Meric-Bernstam  1 , Siqing Fu  1
Affiliations

Modulating Treatment Outcomes of Patients with Solid Tumors in Immunotherapy Trials: A Drug Interaction Analysis from a Phase I Unit

Camila Braganca Xavier et al. Cancer Res Commun. .

Abstract

Purpose: Concurrent use of medications can modulate the effectiveness of immunotherapy. Although this interaction is well documented for immune checkpoint inhibitors, whether this occurs with new experimental compounds has not been evaluated.

Patients and methods: A computerized data extraction tool was used to collect clinical data and identify the prescription of a predefined set of medications within 30 days of immunotherapy infusion in the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center. The primary endpoints were median overall survival (OS) and progression-free survival. Tumor responses were assessed using RECIST.

Results: We identified 897 patients. The most prevalent tumor types were colorectal (24.5%), head and neck (10.5%), and pancreatic (9.4%). The immunotherapy administered consisted of monoclonal antibodies and fusion proteins (64.7%), immune modulators (IM; 20.8%), combinations of IMs and antibodies (9.2%), and oncolytic viruses and cancer vaccines (5.3%). The most frequently prescribed drugs were narcotics (70.5%), antiemetics (49.1%), antihistamines (34.6%), antibiotics (31.2%), and proton pump inhibitors (PPI; 28.7%). Patients receiving antihistamines exhibited increased rates of stable disease and partial response (χ2 8.48; P = 0.014) on the IMs and antibodies combination. The benefit of antihistamines was confirmed in a multivariate analysis of OS [HR, 0.752 (95% CI, 0.603-0.938); P = 0.012]. For patients with colorectal cancer, PPI use was associated with shortened survival, with a median OS of 5.2 months with PPI use and 8.6 months without it (P < 0.001).

Conclusions: Our findings highlight the need for strategies to guide concurrent medication choices for patients receiving immunotherapy in early-phase trials.

Significance: Concurrent administration of antihistamines correlates with enhanced survival in patients receiving experimental immunotherapy for cancer. Conversely, PPI use diminishes survival in patients with colorectal cancer. These findings highlight how tumor immunogenicity and drug interactions can modulate response and survival outcomes, offering new insights to optimize investigational immunotherapy.

PubMed Disclaimer

Conflict of interest statement

A.M. Tsimberidou reports grants and personal fees from OBI Pharmaceuticals; grants from Immatics, ANAVEON, Parker Institute for Cancer Immunotherapy, Novocure, Tempus, MacroGenics, Vividion, Doma Bio, 7 Hills, and AbbVie; and personal fees from BrYet and NEX-I during the conduct of the study. A. Naing reports grants from the NCI, EMD Serono, MedImmune, Healios Onc. Nutrition, Atterocor/Millendo, Amplimmune, ARMO Biosciences, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance Biosciences, Eli Lilly, Kymab, PsiOxus, Arcus Biosciences, NeoImmuneTech, Immune-Onc Therapeutics, Surface Oncology, Monopteros Therapeutics, BioNTech SE, Seven and Eight Biopharma, SOTIO Biotech AG, and GV20 Therapeutics and personal fees from CTI, Deka Biosciences, Janssen Biotech, Mural Oncology, NGM Bio, PsiOxus Therapeutics, Immune-Onc Therapeutics, STCube Pharmaceuticals, OncoSec Keynote-695, Genome and Company, CytomX Therapeutics, Nouscom, Merck Sharp and Dohme Corp, Servier, Lynx Health, AbbVie, Merck, ARMO Biosciences, NeoImmuneTech, NGM Biopharmaceuticals, AKH Inc, The Lynx Group, Society for Immunotherapy of Cancer, KSMO, Scripps Cancer Care Symposium, American Society of Clinical Oncology Direct Oncology Highlights, European Society for Medical Oncology, and CME Outfitters outside the submitted work. D.S. Hong reports that he receives research (inst)/grant funding (inst) from 280 Bio, AbbVie, Adaptimmune, Adlai-Nortye, Amgen, Astellas, AstraZeneca, Bayer, BeiGene USA, BioBridge, Biomea Fusion, Bristol Myers Squibb, Deciphera, E.R. Squibb & Sons LLC, Eisai, Eli Lilly, Endeavor, Erasca, Exelixis Inc., F. Hoffmann-La Roche, Genentech, Immunogenesis, Incyte Inc., Merck, Mirati, NCI-CTEP, Novartis, Pfizer, Quanta Therapeutics, Revolution Medicines, STCube Pharmaceuticals, VM Oncology, and Yiling Pharmaceutical and funding for travel, accommodations, and expenses from the American Association of Cancer Research, the American Society of Clinical Oncology, Bayer, BeiGene USA Inc., Genmab, Medscape, Mirati Therapeutics Inc., Pfizer, Society for the Immunotherapy of Cancer, Telperian Consulting, Speaker, or Advisory Role: 280 Bio, Acuta Capital Partners LLC, Alpha Insights, Amgen, Bayer, Boxer Capital, Children’s Oncology Group, COR2ed, Cowen Group Inc, Crossbridge Bio, Ecor1 Capital, Erasca, Gerson Lehrman Group Inc., Group H, Guidepoint, Immunogenesis, Janssen Pharmaceuticals, Kestrel Therapeutics, Medacorp, Medscape, Orbi Capital, Pfizer, Revolution Medicines, T-Knife, Travistock Group, WebMD, and Yiling Pharmaceutical and that he is the advisor of Molecular Match and CrossBridge Bio and founder and advisor of OncoResponse and Telperian. J. Rodon Ahnert reports that he receives nonfinancial support and reasonable reimbursement for travel from the European Society for Medical Oncology, American Society of Medical Oncology, National Taiwan University Cancer Center, 280-Biotech, Dava Oncology, and STOP Cancer; consulting and travel fees from Ellipses Pharma, IONCTURA, Sardona, Mekanistic, Amgen, Merus, MonteRosa, Aadi, and Bridgebio (including serving on the scientific advisory board); consulting fees from Vall d’Hebron Institute of Oncology, Chinese University of Hong Kong, Boxer Capital, LLC, Tang Advisors, LLC, Guidepoint, and Axiom; and research funding from Blueprint Medicines, Merck Sharp & Dohme, Hummingbird, AstraZeneca, 280 Bio, Vall d’Hebron Institute of Oncology/Cancer Core Europe and serves as an investigator in clinical trials with Cancer Core Europe, Symphogen, BioAlta, Pfizer, Kelun-Biotech, GlaxoSmithKline, Taiho, Roche Pharmaceuticals, Hummingbird, Yingli, Bicycle Therapeutics, Merus, Aadi Bioscience, ForeBio, Loxo Oncology, Hutchinson MediPharma, Ideaya, Amgen, Tango Therapeutics, Mirati, Linnaeus Therapeutics, MonteRosa, Kinnate, Yingli, Debio, BioTheryX, Storm Therapeutics, Beigene, MapKure, Relay, Novartis, FusionPharma, C4 Therapeutics, Scorpion Therapeutics, Incyte, Fog Pharmaceuticals, Tyra, Nuvectis Pharma, Hotspot Pharma, Adcentrix, Vividion, AstraZeneca, Alnylam, Immuneering Corp, Alterome, and Exelixis. P.R. Pohlmann reports grants from Pfizer and personal fees from Pfizer outside the submitted work. S.A. Piha-Paul reports other from ABM Therapeutics Inc., Alkermes, Aminex Therapeutics, Axcynsis Therapeutics Pte.Ltd., BioMarin Pharmaceutical Inc., Boehringer Ingelheim, Chugai Pharmaceutical Co., Ltd., Cyclacel Pharmaceuticals, Daiichi Sankyo Inc., ENB Therapeutics, Epigenetix Inc., Genmab US Inc., Gilead Sciences Inc., Immunity Bio Inc., Immunome Inc., Immunomedics Inc., Incyte Corp., Innovent Biologics Co. Ltd., iTeos Belgium SA, Jazz Pharmaceuticals, Johnson & Johnson, Loxo Oncology Inc., Merck Sharp and Dohme Corp., Mitsubishi Tanabe Pharma America Inc., Nectin Therapeutics, Ltd., Nested Therapeutics Inc., NRG Oncology, Nurix, OncoNano Medicine Inc., Pfizer Pharmaceuticals LLC, Phanes Therapeutics, Pieris Pharmaceuticals Inc., Puma Biotechnology Inc., Purinomia Biotech Inc., Replimune, Roche/Blueprint, Solve Therapeutics Inc., Strand Therapeutics Inc., Tallac Therapeutics Inc., Theradex Oncology, Toragen Therapeutics Inc., TransThera Bio, ViroMissile, Inc., and Xencor Inc. and grants from NCI/NIH P30CA016672 - Core Grant (CCSG Shared Resources), CPRIT Grant - Precision Oncology Decision Support Core (RP150535), and Clinical and Translational Science Award Grant 1UM1TR0045906 outside the submitted work. S. Champiat reports personal fees from Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Genmab, Janssen, Merck KGaA, MSD, Novartis, Roche, and Servier; grants from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bolt Biotherapeutics, Centessa Pharmaceuticals, Cytovation, Eisai, GlaxoSmithKline, Imcheck Therapeutics, Immunocore, Marengo, Molecular Partners AG, MSD, OncoC4, Ose Immunotherapeutics, Pheast, Pierre Fabre, Replimune, Roche, Sanofi Aventis, Seagen, Sotio A.S., and Transgene; other from AccessTrial, Alderaan Biotechnology, Amgen, AstraZeneca, Aummune, Avacta, Bayer, Beigene, BioNTech, Celanese, Compugen, Domain Therapeutics, Ellipses Pharma, Genmab, Immunicom Inc., Mariana Oncology, Mima Health, Nanobiotix, Nextcure, NetCancer, Oncovita, Pharma Mar, Pierre Fabre, Replimune, Seagen, Takeda, Tatum Bioscience, Tollys, UltraHuman8, Avacta, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Ose Immunotherapeutics, Roche, and Sotio outside the submitted work. T.A. Yap reports other from the University of Texas MD Anderson Cancer Center; personal fees from AbbVie, Acrivon, Adagene, Aeneid Therapeutics, Almac, Alterome Therapeutics Inc., Aduro, Amgen Inc., Amphista, Astex, Atavistik, Athena, Atrin, Avenzo, Avoro, Axiom, Baptist Health Systems, Bicycle, BioCity Pharma, Bloom Burton, Bluestar Bio, Boxer, Bristol Myers Squibb, C4 Therapeutics, Calithera, Cancer Research Horizons, Cancer Research UK, Carrick Therapeutics, Clasp, Cybrexa, Daiichi Sankyo, DAiNA, Dark Blue Therapeutics, Dawn Manco, Debiopharm, Diffusion, Duke Street Bio, EcoR1 Capital, Eikon, Ellipses Pharma, Entos, Flagship Pioneering, Forbion, FoRx Therapeutics AG, Genesis Therapeutics, Genmab, Glenmark, GLG, Globe Life Sciences, Grey Wolf Therapeutics, GSK, Guardant, Guidepoint, Idience, Ignyta, I-Mab, Impact Therapeutics, Institut Gustave Roussy, Intellisphere, Jansen, Jazz Pharma, Joint Scientific Committee for Phase I Trials in Hong Kong, Kyn, Kyowa Kirin, Lumanity, MEI Pharma, Mereo, Merit, Monte Rosa Therapeutics, Natera, Nested Therapeutics, Nexus Pharmaceuticals, Nimbus, Novocure, Odyssey Therapeutics, OHSU, OncoSec, Ono Pharma, Onxeo, Piper Sandler, Plexium Inc., Prolynx, Protai Bio, PSIM, Radiopharma Theranostics, resTORbio, Ryvu Therapeutics, SAKK, Schrödinger, Servier, Stablix, Synthis Therapeutics, TCG Crossover, TD2, Techspert.io, Terremoto Biosciences, Tessellate Bio, Theragnostics, Terns Pharmaceuticals, Thryv Therapeutics, Tolremo, Tome Biosciences, Trevarx Biomedical, Varian, Veeva, Versant, Vibliome Therapeutics, Vivace, Voronoi Inc., Xinthera, and Zai Labs; grants and personal fees from Artios, AstraZeneca, Bayer, Beigene, Blueprint, BridGene Biosciences, Circle Pharma, Clovis, 858 Therapeutics, EMD Serono, F-Star, Ideaya Biosciences, ImmuneSensor, Merck, Pfizer, Pliant Therapeutics, Prelude Therapeutics, Repare, Roche, Sanofi, Synnovation, and Tango; and grants from Accent, Aprea Therapeutics, BioNTech, BMS, Boundless Bio, Constellation, CPRIT, Cyteir, Department of Defense, Eisbach Bio, Eli Lilly, Exelixis, Forbius, Gilead, GlaxoSmithKline, Genentech, Golfers Against Cancer, Haihe, Insilico Medicine, Ionis, Ipsen, Jounce, Karyopharm, KSQ, Kyowa, Loxo Oncology, Mirati, Novartis, NIH/NCI, Ribon Therapeutics, Regeneron, Rubius, Scholar Rock, Seattle Genetics, SpringWorks, Tesaro, V Foundation, Vivace, Zenith, and Zentalis outside the submitted work. F. Meric-Bernstam reports personal fees from Sanofi Pharmaceuticals, Lengo Therapeutics, Tallac Therapeutics, Harbinger Health, Clinical Education Alliance, OnCusp Therapeutics, GT Aperion, EcoR1 Capital, Seagen (formerly Seattle Genetics), Mersana, Molecular Templates, Jazz Pharmaceuticals, Menarini Group, eFFECTOR Therapeutics, Becton Dickinson, Zymeworks, Theratechnologies Inc., Scripps Research Institute, Tempus, Guardant Health, Elevation Oncology, Incyte, Go Therapeutics, Kivu Biosciences, AstraZeneca Pharmaceuticals, Exelixis, Illumen, Zentalis Pharmaceuticals, LOXO-Oncology, Biocartis NV, Debiopharm, SystImmune, Ribometrix, Cybrexa Therapeutics, Vir Biotechnology, Protai Bio, LigaChem Biosciences, and Daiichi Sankyo; personal fees and nonfinancial support from Dava Oncology; and nonfinancial support from the European Organisation for Research and Treatment of Cancer, the European Society for Medical Oncology, and the Cholangiocarcinoma Foundation outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.
Associations between antihistamine use and tumor responses. ABS, antibodies; AH, antihistamines; VAC, vaccines.
Figure 2.
Figure 2.
Forest plot for OS (A) and PFS (B) according to multivariate analysis. ATB, antibiotics.
Figure 3.
Figure 3.
Kaplan–Meier OS curves for patients with colorectal cancer receiving PPIs.
See this image and copyright information in PMC

References

    1. Korman AJ, Garrett-Thomson SC, Lonberg N. The foundations of immune checkpoint blockade and the ipilimumab approval decennial. Nat Rev Drug Discov 2022;21:509–28. - PubMed
    1. Zhang Y, Zhang Z. The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell Mol Immunol 2020;17:807–21. - PMC - PubMed
    1. Bessede A, Marabelle A, Guégan JP, Danlos FX, Cousin S, Peyraud F, et al. Impact of acetaminophen on the efficacy of immunotherapy in cancer patients. Ann Oncol 2022;33:909–15. - PubMed
    1. Stefani A, Bria E. Is immunotherapy with concomitant proton pump inhibitor use a viable combination? JAMA Netw Open 2023;6:e2322922. - PubMed
    1. Li H, Xiao Y, Li Q, Yao J, Yuan X, Zhang Y, et al. The allergy mediator histamine confers resistance to immunotherapy in cancer patients via activation of the macrophage histamine receptor H1. Cancer Cell 2022;40:36–52.e9. - PMC - PubMed

Substances