Primary results of STRONG: An open-label, multicenter, phase 3b study of fixed-dose durvalumab monotherapy in previously treated patients with urinary tract carcinoma

Abstract

Background: Prior durvalumab (anti-PD-L1 agent) studies in platinum-refractory metastatic urothelial carcinoma evaluated a dose of 10 mg/kg administered every two weeks. The nonrandomised phase 3b STRONG study (NCT03084471) evaluated the safety and efficacy of fixed-dose durvalumab at a more convenient dosing schedule in a previously treated patient population, more similar to a real-world clinical setting.

Patients and methods: 867 patients with urothelial or nonurothelial urinary tract carcinoma (UTC) who progressed on or after platinum or nonplatinum chemotherapy were treated with durvalumab 1500 mg every four weeks; 87% had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, and 13% had an ECOG PS of 2. The primary end-point was the incidence of adverse events of special interest (AESIs), including immune-mediated AEs (imAEs). Secondary and exploratory end-points included overall survival (OS), objective response rate (ORR) and disease control rate (at six and 12 months) (DCR).

Results: AESIs of any grade were reported in 51% of patients (8% grade ≥ 3). The incidence of imAEs was 11% (2% grade ≥ 3). The median OS was 7.0 months (95% confidence interval [CI]: 6.4-8.2) and ORR was 18% (95% CI: 14.8-20.6), with complete responses in 5% of patients and a DCR at six months of 19% (95% CI: 16.1-22.1).

Conclusion: Fixed-dose durvalumab monotherapy every four weeks has an acceptable safety profile and yields durable clinical activity in previously chemotherapy-treated patients with UTC. Safety and efficacy are consistent with previous durvalumab studies and other anti-PD-1/PD-L1 agents in this setting. CLINICALTRIALS.

Gov identifier: NCT03084471https://ichgcp.net/clinical-trials-registry/NCT03084471.

Keywords: Adverse events of special interest; Durvalumab; Fixed dose; Immune checkpoint inhibitor; Immune-mediated adverse events; Immune-related adverse events; Overall survival; PD-L1; Urinary tract carcinoma; Urothelial carcinoma.

Conflict of interest statement

Conflict of interest statement The following authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper: Sang Joon Shin and Guilhem Roubaud. The following authors declare the following financial interests/personal relationships that may be considered as potential competing interests: Guru P. Sonpavde: Has received grants or contracts (institution) from AstraZeneca, Janssen, and Sanofi; Consulting fees from Astellas Pharma, AstraZeneca, Bicycle Therapeutics, Bristol-Myers Squibb, Eisai, EMD Serono, Exelixis, Genentech, Janssen, Merck, Pfizer and Seattle Genetics; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Medscape, Onclive, Physicans' Education Resource and Research to Practice; Support for attending meetings and/or travel from Bristol-Myers Squibb; Other financial or non-financial interests from Astellas Pharma, AstraZeneca, Bavarian Nordic, Bristol-Myers Squibb, Debiopharm Group, Elsevier and QED Therapeutics. Cora N. Sternberg: Has received consulting fees from Astellas Pharma, AstraZeneca, Bayer, Genzyme, Immunomedics, Incyte, Medscape, Merck, Merck Sharp & Dohme, Pfizer, Roche and UroToday. Yohann Loriot: Has received grants or contracts (institution) from AstraZeneca, Boehringer Ingelheim, Clovis Oncology, CureVac, Exelixis, Incyte, Janssen Oncology, Medivation, Merck Sharp & Dohme Oncology, Nektar, Oncogenex, Pfizer and Sanofi; Consulting fees from Astellas Pharma, AstraZeneca; Clovis Oncology, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme Oncology, Roche and Seattle Genetics and institution consulting fees from Janssen and Merck Sharp & Dohme Oncology; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Pfizer and Sanofi; Support for attending meetings and/or travel Astellas Pharma, AstraZeneca; Janssen Oncology, Merck Sharp & Dohme Oncology, Roche and Seattle Genetics. Jae Lyun Lee: Has received grants or contracts (institution) from AstraZeneca/MedImmune, Bayer Schering Pharma, Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis, Pfizer and Roche/Genentech and Seattle Genetics; Consulting fees from Alteogen, Bristol-Myers Squibb, GI Innovation, Merck Sharp & Dohme, Pfizer and Sanofi/Aventis; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme and Pfizer; Stock or stock options from Immunomedics and Myovant Sciences. Aurelien Marabelle: Has received grants or contracts (institution) from Boehringer Ingelheim, Bristol-Myers Squibb, MERUS, MSD and Transgene; Consulting fees from AstraZeneca Bayer, Boehringer Ingelheim, CERENIS THERAPEUTICS, Eisai, Gritstone Oncology, HiFiBiO Therapeutics, ImCheck therapeutics, Innate Pharma, Lytix Biopharma, Merck Serono, Molecular Partners, Merck Sharp & Dohme, OSE Immunotherapeutics, Pierre Fabre, Redx Pharma, Roche, Sanofi, SERVIER, Sotio, Symphogen; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme; Support for attending meetings and/or travel from AstraZeneca and Merck Sharp & Dohme; Patents planned, issued or pending from Stanford University (Monoclonal antibodies against CD81); Stock or stock options from HiFiBiO Therapeutics and PEGASCY and PEGASCY (insitition); Other financial or non-financial interests from PEGASCY; Honoraria received from Elsevier as an editor for the European Journal of Cancer. AudeFléchon: Has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events and/or support for attending meetings and/or travel rom Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Ipsen, Janssen-Cilag, Merck Sharp & Dohme Oncology, Pfizer, Roche/Genentech and Sanofi/Aventis. Damien Pouessel: Has received has received grants or contracts (institution) from AstraZeneca, Bristol-Myers Squibb, Incyte, Janssen Oncology, Merck Sharp & Dohme, Roche and Seattle Genetics; Consulting fees from Astellas Pharma, AstraZeneca, Janssen Oncology, Pfizer and Sanofi; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen Oncology and Merck; Support for attending meetings and/or travel from AstraZeneca, Janssen Oncology and Pfizer. Vittorina Zagonel: Has received has received grants or contracts (institution) from Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Ipsen, Lilly and Roche; Consulting fees from Bristol-Myers Squibb and Merck; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Lilly, Roche and Servier; Support for attending meetings and/or travel from Bayer, Roche and Servier. Fabio Calabro: Has received consulting fees from Merck Sharp & Dohme Oncology and Pfizer. Giuseppe L. Banna: Has received consulting fees from AstraZeneca, Boehringer Ingelheim, Janssen-Cilag and Roche; Support for attending meetings and/or travel from AstraZeneca/MedImmune, Bristol-Myers Squibb, Ipsen and Pierre Fabre; Patents planned, issued or pending with ST Microelectronics “Deep Learning Motion Algorithm for Lung Cancer Early Detection in Embedded Systems” and “Image processing method, corresponding system and computer program product”. Francisco E. Vera-Badillo: Has received grants or contracts (institution) from AstraZeneca/MedImmune. Thomas Powles: Has received has received grants or contracts, consulting fees and/or payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Eisai, Exelixis, Incyte, Ipsen, Johnson & Johnson, Merck, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche and Seattle Genetics; Support for attending meetings and/or travel from AstraZeneca, Ipsen, Merck Sharp & Dohme, Pfizer and Roche. Eva Hellmis: Has received support for attending meetings and/or travel from Janssen-Cilag. Paulo A. P. Miranda is a current employee of AstraZeneca with AstraZeneca stock or stock options. Ugochi Emeribe and Sun Min Oh are current employees of AstraZeneca. Ana Rita Lima is currently employed as a Third Party Service Provider to AstraZeneca. Sebastien J. Hotte: Has received grants or contracts (institution) from Astellas Pharma, AstraZeneca, Ayala Pharmaceuticals, Bristol-Myers Squibb, Clovis Oncology, Janssen Oncology, Merck, Pfizer, Roche/Genentech, Seattle Genetics and SignalChem; Consulting fees from Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Ipsen, Janssen, Merck, Pfizer and Roche Canada; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas Scientific and Medical Affairs Inc, Bayer, Janssen Oncology and Merck; Support for attending meetings and/or travel from Eisai.

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