Response and Survival With Immune Checkpoint Inhibitor in Patients With Advanced Urothelial Carcinoma and Histology Subtypes
- PMID: 40378559
- DOI: 10.1016/j.clgc.2025.102356
Response and Survival With Immune Checkpoint Inhibitor in Patients With Advanced Urothelial Carcinoma and Histology Subtypes
Abstract
Background: Immune Checkpoint Inhibitors (ICIs) are used for advanced urothelial carcinoma (aUC) in different settings. Most patients have pure UC (PUC) but about one-third have UC mixed with histology subtypes (HS). We examined outcomes in patients with HS aUC treated with ICI.
Materials and methods: We included patients from 26 centers with PUC and any HS treated with ICI as 1st line (1L) upfront, maintenance avelumab (mAV), and ≥2nd line [2+L] therapy. We calculated overall and progression-free survival (OS, PFS) and observed response rate (ORR) from ICI start.
Results: We included 1511 patients; 752 1L, 609 2+L, 150 mAV. 1L: median OS was 15 (95% CI, 12-17) months for patients with PUC (n = 518), 15 (95% CI, 8-23) months for squamous UC (n = 85) (HR = 1.2, [95% CI, 0.8-1.6]), 11 (95% CI, 6-17) months for micropapillary UC (n = 46) (HR = 1.2, [95% 0.8-1.8]), and 21 (95% CI, 12-30) months in patients with UC mixed with ≥2 HS (n = 30), (HR = 0.9, [95% CI, 0.5-1.4]). 2+L: median OS was 9 (95% CI, 8-10) months for patients with PUC (n = 441), 9 (95% CI, 1-12) months for squamous UC (n = 60) (HR = 1.1, (95% CI, 0.8-1.6]), 6 (95% CI, 1-11) months for micropapillary UC (n = 37) (HR = 1.1, [95% 0.7-1.6]), and 7 (95% CI, 4-10) months in patients with UC mixed with ≥2 HS (n = 17), (HR = 1.6, [95% CI, 0.9-3.1]).
Conclusion: We found no significant OS difference between PUC and HS in patients with aUC treated with ICI monotherapy. Limitations include retrospective design, small sample size in several subsets, lack of randomization, no central imaging or pathology review, selection and confounding biases. Results are hypothesis-generating and need prospective validation.
Keywords: Bladder cancer; Immunotherapy; Outcomes; Variant; Variant histology.
Copyright © 2025 Elsevier Inc. All rights reserved.
Conflict of interest statement
Disclosure Dimitra Rafailia Bakaloudi, Thomas Enright, Jacob B. Leary, Dimitrios Makrakis, Leonidas N. Diamantopoulos, Charbel Hobeika, Vinay Mathew Thomas, Roubini Zakopoulou, Tanya Jindal, Jure Murgić, Marija Miletić, Ana Frobe, Charles Latchford, Jeffrey Johnson, Gavin Hui, Alejo Rodriguez-Vida, Macarena Rey-Cárdenas, Lucia Alonso Buznego, David Marmolejo Castañeda, Clara Castro Carballeira, Ilana B. Epstein, Ruben Raychaudhuri, Rosa Nadal, Funda Vakar-Lopez: No relevant conflicts to disclose. Rafee Talukder: Consulting or advisory: AstraZeneca, Pfizer, IDEOlogy Umang Swami: consultancy to Astellas, AstraZeneca, Adaptimmune, Exelixis, Gilead, Imvax, Janssen, Pfizer, Seattle Genetics and Sanofi and research funding to institute from Janssen, Exelixis and Astellas/Seattle Genetics. Aristotelis Bamias: Honoraria, Advisory role, research support by BMS, MSD, AZ, Pfizer. Jason R. Brown: Advisory Boards: EMD-Serono, Pfizer, Janssen. Received funding from EMD-Serono and Merck for a Speaker’s Bureau. David Pinato: Lecture fees: Bayer Healthcare, Astra Zeneca, EISAI, Bristol Myers-Squibb, Roche, Boston Scientific, Ipsen; Travel expenses: Bristol Myers-Squibb, Roche, Bayer Healthcare, Astra Zeneca; Consulting fees: Mina Therapeutics, Galapagos, Parabilis, Boeringer Ingelheim, Ewopharma, EISAI, Ipsen, Roche, H3B, Astra Zeneca, DaVolterra, Mursla, Avammune Therapeutics, Starpharma, LiFT Biosciences, Exact Sciences; Research funding (to institution): MSD, BMS, GSK. Vadim S. Koshkin: has served in a consulting or advisory role for Astellas, Bicycle Therapeutics, BMS, Janssen, Loxo Oncology, MSD, Pfizer/Seagen, Roche/Genentech, Tempus. Research funding from Astellas, Curium, Eli Lilly, Endocyte/Novartis, Gilead, Merck, Seagen/Pfizer, Taiho and the Prostate Cancer Foundation. Yousef Zakharia: Advisory Board: Bristol Myers Squibb, Amgen, Roche Diagnostics, Novartis, Janssen, Eisai, Exelixis, Castle Bioscience, Genzyme Corporation, Astrazeneca, Array, Bayer, Pfizer, Clovis, EMD serono, Myovant. Grant/research support from: Institution clinical trial support from NewLink Genetics, Pfizer, Exelixis, Eisai. DSMC: Janssen Research and Development.Consultant honorarium: Pfizer, Novartis. Ajjai Alva: Dr. Ajjai Alva serves as a consultant for Merck, AstraZeneca, Bristol-Myers Squibb, and Pfizer/EMD Serono. Dr. Ajjai Alva receives research funding through the University of Michigan from Merck, Genentech, Prometheus Laboratories, Mirati Therapeutics, Roche, Bayer, Progenics, Astellas Pharma, Arcus Biosciences, AstraZeneca, Bristol-Myers Squibb, and Clovis Oncology. Charles B. Nguyen: Honorarium: OncLive and DAVA Oncology. Alexandra Drakaki has served as consultant for Bristol-Myers Squibb, AstraZeneca, RADMETRIX, Seattle Genetics, Janssen, PACT Pharma, Merck, Roche/Genentech, Exelixis, Dyania Health, has received research funding from Kite/Gilead, AstraZeneca, Genentech/Roche, BMS, Merck Sharp & Dohme, Jounce Therapeutics, Infinity Pharmaceuticals, Seattle Genetics/Astellas, and has received travel expenses from Lilly, AstraZeneca and Seattle Genetics. Daniel Castellano: Consulting or Advisory Role: Janseen Oncology, Roche/Genentech, Astellas Pharma, AstraZeneca, Pfizer, Novartis, Ipsen, Bristol-Myers Squibb, MSD Oncology, Bayer, Lilly, Sanofi, Pierre Fabre, Bpehringer Ingelheim. Research funding: Janseen Oncology. Travel, Accomondations, Expenses: Pfizer, Roche, Bristol-Myers Squibb, AstraZeneca Spain. Ignacio Duran: Research Grant to institution: Roche, AstraZeneca, Honoraria: Bristol Myers Squibb, MSD, Ipsen, Roche-Genentech, Janssen, Astellas Pharma, EUSA Pharma, Bayer, Novartis, Gilead, Bayer. Support for attending meetings and/or travel: Merck-Pfizer, Ipsen, Jansen, Bayer, AstraZeneca. Advisory board: Bristol Myers Squibb, MSD, Ipsen, Roche-Genentech, Astellas Pharma, EUSA Pharma, Bayer, Novartis, Eisai, Debio Pharma, Pharmacyclycs, Gilead. Rafael Morales-Barrera has served as consultant/advisor for Sanofi, AstraZeneca, Astellas Pharma and MSD, has been in the speaker’s Bureau for Astellas Pharma, Merck/Pfizer and MSD Oncology, and has received travel accommodations from Sanofi, Pfizer, MSD, Astellas Pharma, Astra Zeneca, Bayer, Roche/Genentech. Rana R. McKay: Consulting/Advisory Board – Aveo, AstraZeneca, Bayer, Bristol Myers Squib, Calithera, Caris, Denderon, Exelixis, Esiai, Janssen, Lilly, Merck, Myovant, Novartis, Pfizer, Sanofi, SeaGen, Sorrento Therapeutics, Telix, Tempus. Institutional Research Funding – Bayer, Tempus, AstraZeneca, Oncternal, Exelixis, BMS. Tyler F. Stewart Advisory Board for Pfizer, Astellas, Seagen, Astrazeneca, EMD Serono. Research Grants from GRAIL. Pedro Barata: reports grants or personal fees from Astellas; AstraZeneca; Bayer; BMS; Caris Life Sciences; Guardant Health; Eisai; EMD Serono; ESSA Pharma; Exelixis; Ipsen; Janssen; Merck; Merus; Novartis; Myovant; UroToday; OncLive; Pfizer, Seattle Genetics; Targeted Oncology Joaquim Bellmunt: received advisory/consulting fees from Astellas Pharma, AstraZeneca/MedImmune, Bristol-Myers Squibb, Genentech, Merck, Pfizer,Takeda and Pierre Fabre, research funding support from Millennium, Sanofi and Pfizer/EMD Serono;trial sponsorship through Associació per a la RecercaOncológia (APRO), royalties from UpToDate, stocks from Rainier Therapeutics, and a nonfinancial interest as President of APRO. Evan Y. Yu Consultancy to Advanced Accelerator Applications, Aadi Bioscience, Bayer, Bristol-Myers Squibb, Janssen, Lantheus, Loxo, Merck, and Oncternal. Research funding to Evan Yu’s institution: Bayer, Blue Earth, Dendreon, Lantheus, Merck, Oncternal, Seagen and Tyra. Shilpa Gupta Consultancy: Bristol Myers Squibb, Merck, Janssen, Seattle Genetics, Pfizer, Astellas, Novartis, Foundation Medicine, EMD Sorono; speaker for Bristol Myers Squibb; Institutional grants from Exelixis, Bristol Myers Squibb, Merck, Flare Therapeutics, Roche, Novartis, Tyra Biosciences, Pfizer, Convergent Therapeutics. Jonathan L. Wright: Royalties – UpToDate; Clinical Trials/Research - Merck, Nucleix, Altor Biosciences, Pacific Edge, Seagen, Janssen, Veracyte; Consulting – ImmunityBio; Pacific Edge. Ali Raza Khaki has received institutional research funding from 23andMe, Pfizer, Janssen, and Acrivon Therapeutics, and has had uncompensated relationships with Pfizer/Astellas and Janssen. Petros Grivas: in last 2 years, reports consulting with MSD, Bristol Myers Squibb, AstraZeneca, EMD Serono, Pfizer, Janssen, Roche, Astellas Pharma, Gilead Sciences, Fresenius Kabi, Strata Oncology, ImmunityBio, Asieris Pharmaceuticals, AbbVie, Bicycle Therapeutics, Replimune, Daiichi Sankyo, Eli Lilly, and research funding from Bristol-Myers Squibb, MSD, QED Therapeutics, EMD Serono, Gilead Sciences, Acrivon Therapeutics, ALX Oncology, Genentech (paid to their institution).