Impact of Angiotensin Converting Enzyme Inhibitors on Pathologic Complete Response With Neoadjuvant Chemotherapy for Muscle Invasive Bladder Cancer.

The renin-angiotensin system (RAS) has been demonstrated to modulate cell proliferation, desmoplasia, angiogenesis and immunosuppression. We examined the association of RAS inhibitors (RASi)-namely angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB)-with neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) preceding radical cystectomy (RC). We retrospectively investigated concurrent RASi use with NAC prior to RC in 302 patients with MIBC from 3 academic institutions. Outcomes included pathologic complete response (pCR) and overall survival (OS). Pathologic features, performance status (PS), clinical stage, type/number of cycles of NAC, and toxicities were collected. Overall pCR rate was 26.2% and 5-year OS was 62%. Concurrent ACEi intake with NAC approached significance for association with pCR (odds ratio [OR] = 1.71; 95% CI, 0.94-3.11; P = .077). Patients with cT3/4N0-N1 disease receiving ACEi had higher pCR rates (30.8% vs. 17.7%, P = .056) than those not on ACEi. Female sex had a statistically significant favorable interaction for pCR with ACEi intake (P = .044). ACEi intake was not associated with OS, while pCR, PS and lower clinical stage were significantly associated with improved OS. ACEi intake is potentially associated with increased pCR in patients with MIBC receiving NAC prior to RC, and this association is more pronounced in patients with higher clinical stage of disease at the initiation of therapy and female sex. Our data suggest the potential relevance of the RAS as a therapeutic target in aggressive MIBC.

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Disclosure Parvaneh Fallah Scientific advisor/consultant: BMS, Seagen, Pfizer, Astrazeneca, EMD Sereno Canada Honoraria: Astrazeneca, EMD Sereno Canada, Gilead, Merck, Janssen Rohit K Jain Receiving honoraria from FLASCO, Curio Science, DAVA Oncology, NCCN/Pfizer, and OncLive/MJH Life Sciences Consulting for AVEO, Bristol Myers Squibb, Sanofi, EMD Serono, Gilead Sciences, IDEOlogy Pfizer, and Seattle Genetics/Astellas In the speakers’ bureau of Gilead Sciences, Seagen, and Seattle Genetics/Astellas Receiving research funding from Bristol Myers Squibb, Gilead Sciences, and NCI. Praful Ravi Research funding to institution: Lilly, Bayer, Telix Speaker's fees: OncLive Charlene Mantia Consulting/advisory role: Aadi Bioscience, Synthekine, Nextech Institutional research funding: Bristol Myers Squibb Bradley Alexander McGregor Received funds for consulting: Arcus, BMS, Eisai, Exelixis, Gliead, Pfizer, SeaGen Funding to institution - BMS, Exelixis, Gilead, Pfizer, SeaGen Roger Li Research support: Predicine; Veracyte; CG Oncology; Valar labs; Merck. Clinical trial protocol committee: CG Oncology; Merck; Janssen. Scientific advisor/consultant: BMS, Merck, Fergene, Arquer Diagnostics, Urogen Pharma, Lucence, CG Oncology, Janssen, Thericon. Honoraria: SAI MedPartners, Solstice Health Communications, Putnam Associates, UroToday. Wassim Kassouf Consultant or advisory roles: Sesen Bio, Ferring, Roche, BMS, Merck, Janssen, Bayer, Astellas, Seagen, Pfizer/EMD Serono, Photocure Clinical trials: BMS, Roche, Janssen, Theralase, Pfizer, CG Oncology Gregory Russell Pond Received honorariums from Astra-Zeneca and Takeda Received consulting fees from Merck and Profound Medical. Close family member who is employed by Roche Canada, and who owns stock in Roche Ltd. Raskesh K. Jain Received consultant fees from Cur, DynamiCure, Elpis, Merck, SPARC, SynDevRx Owns equity in Accurius, Enlight, SynDevRx Served on the Boards of Trustees of Tekla Healthcare Investors, Tekla Life Sciences Investors, Tekla Healthcare Opportunities Fund, Tekla World Healthcare Fund Received grants from Boehringer Ingelheim and Sanofi. Research is supported by NIH R01CA259253, R01CA269672, R01-NS118929, U01CA261842, and grants from the National Foundation for Cancer Research, Jane's Trust Foundation, Niles Albright Research Foundation, and Harvard Ludwig Cancer Center. Guru Sonpavde Advisory Board: EMD Serono, BMS, Merck, Seattle Genetics/Astellas, Janssen, Bicycle Therapeutics, Pfizer, Gilead, Scholar Rock, Eli Lilly/Loxo Oncology, Vial, PrecisCa, Atkis, Kura Oncology, Daiichi-Sankyo Consultant/Scientific Advisory Board (SAB): Syapse, Merck, Servier, Syncorp Research Support to institution: EMD Serono, Jazz Therapeutics, BMS Speaker: Seagen, Gilead, Natera, Exelixis, Janssen, Astellas, Bayer, Aveo, Merck, Pfizer Data safety monitoring committee (honorarium): Mereo Employment: Spouse employed by Myriad Travel: BMS, Astellas