Erdafitinib versus pembrolizumab in pretreated patients with advanced or metastatic urothelial cancer with select FGFR alterations: cohort 2 of the randomized phase III THOR trial.

BACKGROUND

Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor approved to treat locally advanced/metastatic urothelial carcinoma (mUC) in patients with susceptible FGFR3/2 alterations (FGFRalt) who progressed after platinum-containing chemotherapy. FGFR-altered tumours are enriched in luminal 1 subtype and may have limited clinical benefit from anti-programmed death-(ligand) 1 [PD-(L)1] treatment. This cohort in the randomized, open-label phase III THOR study assessed erdafitinib versus pembrolizumab in anti-PD-(L)1-naive patients with mUC.

PATIENTS AND METHODS

Patients ≥18 years with unresectable advanced/mUC, with select FGFRalt, disease progression on one prior treatment, and who were anti-PD-(L)1-naive were randomized 1 : 1 to receive erdafitinib 8 mg once daily with pharmacodynamically guided uptitration to 9 mg or pembrolizumab 200 mg every 3 weeks. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety.

RESULTS

The intent-to-treat population (median follow-up 33 months) comprised 175 and 176 patients in the erdafitinib and pembrolizumab arms, respectively. There was no statistically significant difference in OS between erdafitinib and pembrolizumab [median 10.9 versus 11.1 months, respectively; hazard ratio (HR) 1.18; 95% confidence interval (CI) 0.92-1.51; P = 0.18]. Median PFS for erdafitinib and pembrolizumab was 4.4 and 2.7 months, respectively (HR 0.88; 95% CI 0.70-1.10). ORR was 40.0% and 21.6% (relative risk 1.85; 95% CI 1.32-2.59) and median duration of response was 4.3 and 14.4 months for erdafitinib and pembrolizumab, respectively. 64.7% and 50.9% of patients in the erdafitinib and pembrolizumab arms had ≥1 grade 3-4 adverse events (AEs); 5 (2.9%) and 12 (6.9%) patients, respectively, had AEs that led to death.

CONCLUSIONS

Erdafitinib and pembrolizumab had similar median OS in this anti-PD-(L)1-naive, FGFR-altered mUC population. Outcomes with pembrolizumab were better than assumed and aligned with previous reports in non- FGFR-altered populations. Safety results were consistent with the known profiles for erdafitinib and pembrolizumab in this patient population.

Informations de copyright

Copyright © 2023 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure AOS has received honoraria from Astellas, AstraZeneca, Bavarina Nordic, Basilea, Bicycle Therapeutics, Bristol Myers Squibb, G1 Therapeutics, Genentech, Gilead, Ideeya Biosciences, Immunomedics, Janssen, Loxo, Merck, Mirati, Nektar, Seattle Genetics, and Taiho and research funding (institutional) from Basilea Pharmaceutica, Bristol Myers Squibb, Janssen, Loxo, Merck, Millennium, and Nektar. NM has received honoraria (personal) from Sanofi; research funding (institutional) from Amgen, Astellas Pharma, AstraZeneca, Bayer, Chugai Pharm, Eisai, Janssen, Lilly, Merck Sharp & Dohme, Pfizer, PRA Health Science, Roche, Seagen, Taiho, and Takeda; and has been reimbursed for travel, accommodations, or expenses (personal) from Pfizer. SHP has received honoraria from Merck, Ono Pharma Korea, and Pfizer; served as a consultant for Janssen Oncology; and received institutional research support from Merck Sharp & Dohme. RAH has received personal fees from Aspen Parkside Hospital, Merck, and Pfizer; consulting fees from Bristol Myers Squibb, Roche, Merck Sharp & Dohme, Janssen Oncology, Nektar, and Bayer; honoraria from Janssen Oncology; has been reimbursed for travel, accommodations, or expenses from Janssen Oncology, Roche/Genentech, MSD Oncology, and Nektar; has other financial or non-financial interests with Merck Sharp & Dohme, Roche, Bristol Myers Squibb, and Janssen; and has a leadership or fiduciary role at Cancer Clinic London Liability Partnership, outside of the submitted work. EFB has received honoraria from Exelixis, Janssen, Merck, Novartis, and Pfizer; research funding (personal) from Astellas and Pfizer; and research funding (institutional) from Astellas, Bristol Myers Squibb, Janssen, Merck, Pfizer, Roche/Genentech, and Seagen. NH has received consulting fees from Astellas, AstraZeneca, Bristol Myers Squibb, Gilead, Janssen, Merck, and Pfizer. MO has served as a consultant for Sanofi, Astellas, and Bayer; has participated in a speaker’s bureau for Regeneron; and has been reimbursed for travel, accommodation, and expenses by Sanofi and Regeneron. BPV has served as a consultant for Astellas Pharma, Astra Zeneca, Bayer, Bristol Myers Squibb, and Novartis; has received honoraria from Astellas, Bristol Myers Squibb, Eusa Pharma, Ipsen, Merck Sharp & Dohme, Pierre Fabre, Pfizer, and Roche; and has been reimbursed for travel, accommodations, or expenses by Bristol Myers Squibb, Janssen-Cilag, Merck, Novartis, and Pfizer. BL has received honoraria from Janssen and has been reimbursed for travel, accommodations, or expenses by Astellas, Jassen, and Pfizer. UB has participated in a speaker’s bureau for and/or received travel and accommodation grants from Astellas, AstraZeneca, Bristol Myers Squibb, Ipsen, Janssen, and Merck Sharp & Dohme and has received research funding (institutional) from Ipsen. YK serves as a functional service provider for Janssen. ST, SA, KD, and SM are employed by Janssen Research & Development and have stock or stock options with Johnson & Johnson. YL has received consulting fees from Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Immunomedics, Janssen (and institutional), MSD Oncology (and institutional), Loxo/Lilly, Pfizer/EMD Serono, Roche, and Taiho Pharmaceutical; has been reimbursed for travel, accommodations, or expenses from Astellas, AstraZeneca, Janssen Oncology, MSD Oncology, and Roche; and has received research funding (institutional) from Astellas Pharma, AstraZeneca, Basilea, Bristol Myers Squibb, Exelixis, Gilead Sciences, Incyte, Janssen Oncology, Merck KGaA, MSD Oncology, Nektar, Pfizer, Roche, Sanofi, and Taiho Pharmaceutical.