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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

2023; Elsevier BV; Volume: 35; Issue: 1 Linguagem: Inglês

10.1016/j.annonc.2023.10.003

1569-8041

Arlene O. Siefker‐Radtke, Nobuaki Matsubara, S.H. Park, Robert Huddart, Earle F. Burgess, Mustafa Özgüroğlu, Begoña P. Valderrama, Brigitte Laguerre, Umberto Basso, Spyros Triantos, Sydney Akapame, Yin Kean, K. Deprince, S. Mukhopadhyay, Yohann Loriot, Patricia Bastick, Sanjeev Sewak, Ben Tran, Martin Pichler, Shahrokh F. Shariat, Sylvie Rottey, Peter Schatteman, Dirk Schrijvers, Vincent Verschaeve, Christof Vulsteke, Luiza Aleixo Barros Leite Ferreira, Pereira de Santana Gomes Andrea Juliana, João P. M. António, Sérgio Jobim Azevedo, Diogo Bastos, Giuliano Santos Borges, Aldo Lourenço Abbade Dettino, Pires Luis Antonio, Murilo Luz, Suelen Bianca Stopa Martins, José Maurício Mota, J M Octavio de Toledo, Bernhard J. Eigl, Daygen L. Finch, Joel Gingerich, Haiying Dong, Jian Huang, Jie Jin, Hongming Pan, Zhongquan Sun, Ye Tian, Ben Wan, Bin Wu, Ting Xu, Wei Xue, Fangjian Zhou, Philippe Barthélémy, Delphine Borchiellini, Fabien Calcagno, Aurélien Carnot, Pierre Cornillon, R. Delva, Sheik Emambux, Nadine Houédé, Brigitte Laguerre, Géraldine Lauridant, Yohann Loriot, Hakim Mahammedi, Denis Maillet, Damien Pouessel, Guilhem Roubaud, Friederike Schlürmann-Constans, Diégo Tosi, Sylvie Zanetta, Séverine Banek, Susan Feyerabend, Mario W. Kramer, Guenther Niegisch, Philipp Nuhn, Marco J. Schnabel, Christian Wuelfing, Sofia Baka, Aristotelis Bamias, George Fountzilas, Harabolos Kalofonos, Konstantinos Karalis, Athanasios Κotsakis, Eleni Timotheadou, László Landherr, László Mangel, Avivit Peer, Meital Levratovsky, Umberto Basso, Nicola Battelli, Alessia Cavo, Ugo De Giorgi, Laura Doni, Luca Galli, Maria Olga Gigante, Valentina Guadalupi, Michele Maio, Laura Milesi, Franco Nolè, Giorgio V. Scagliotti, Giampaolo Tortora, Satoshi Fukasawa, Toru Harabayashi, Naoto Kamiya, Takashi Kawahara, Mutsushi Kawakita, Nobunaki Matsubara, Kazumasa Matsumoto, Kazuo Nishimura, Rikiya Taoka, Nobuaki Shimizu, T. Tagaki, Taek Won Kang, Jwa Hoon Kim, S.H. Kim, Hyo Jin Lee, Yun‐Gyoo Lee, Sun Young Rha, Ho Kyung Seo, Maartje Los, Bogdan Żurawski, Paulo Cortes, C. Faustino, Nuno Vau, Ricardo da Luz, Vagif Atduev, Dmitry Kirtbaya, Evgeny Kopyltsov, А. П. Лыков, Urmantsev Marat, Sergey Orlov, Konstantin Penkov, Albert Pirmagomedov, Andrey Semenov, Sergey Varlamov, Geòrgia Anguera, Montserrat Domènech, Regina Gironés, Aranzazu González del Alba, Nuria Laínez Milagro, Raquel Luque, Esther Ortega, Begoña Mellado, M.J. Méndez Vidal, Esteban Nogales Fernandez, Begoña P. Valderrama, Álvaro Pinto Marín, Carmen Santander, Eric Yi‐Hsiu Huang, Wen-Pin Su, Hung-Chan Wu, Wen‐Jeng Wu, Kai‐Jie Yu, Ahmet Bılıcı, Erdem Göker, Mahmut Gümüş, Aziz Karaoğlu, Umut Kefeli, Fatih Köse, Mustafa Özgüroğlu, Deniz Tural, Hacı Mehmet Türk, Şuayib Yalçın, Igor Bondarenko, Геннадій Хареба, Yana Kidik, Oleksandr Lychkovskyy, V.S. Sakalo, Serghii Shevnia, Eduard Stakhovskyy, Amit Bahl, Simon J. Crabb, Thomas Powles, Peter Sankey, Mohammad Sarwar, Pasquale Benedetto, Earle F. Burgess, Nancy A. Dawson, Gurjyot K. Doshi, Mark T. Fleming, Joseph Maly, Mamta Parikh, David Waterhouse,

Fibroblast Growth Factor Research

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 ( FGFR alt ) 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.