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

A. O. Siefker-Radtke, N. Matsubara, S. H. Park, R. A. Huddart, E. F. Burgess, M. Ozguroglu, B. P. Valderrama, B. Laguerre, U. Basso, S. Triantos, S. Akapame, Y. Kean, K. Deprince, S. Mukhopadhyay, Y. Loriot, P. Bastick, S. Sewak, B. Tran, M. Pichler, S. ShariatS. Rottey, P. Schatteman, D. Schrijvers, V. Verschaeve, C. Vulsteke, L. A. Barros Leite Ferreira, P. de Santana Gomes Andrea Juliana, J. A. Junior, S. Azevedo, D. Bastos, G. Borges, A. Dettino, P. L. Antonio, M. Luz, S. Martins, J. M. Mota, J. Toledo, B. Eigl, D. Finch, J. Gingerich, H. Dong, J. Huang, J. Jin, H. Pan, Z. Sun, Y. Tian, B. Wan, B. Wu, T. Xu, W. Xue, F. Zhou, P. Barthelemy, D. Borchiellini, F. Calcagno, A. Carnot, P. Cornillon, R. Delva, S. Emambux, N. Houede, B. Laguerre, G. Lauridant, Y. Loriot, H. Mahammedi, D. Maillet, D. Pouessel, G. Roubaud, F. Schlurmann-Constans, Domiziano Dario Tosi, S. Zanetta, S. Banek, S. Feyerabend, M. Kramer, G. Niegisch, P. Nuhn, M. Schnabel, C. Wuelfing, S. Baka, A. Bamias, G. Fountzilas, H. Kalofonos, K. Karalis, A. Kotsakis, E. Timotheadou, L. Landherr, L. Mangel, A. Pe'Er, M. Levratovsky, U. Basso, N. Battelli, A. Cavo, U. De Giorgi, L. Doni, L. Galli, M. O. Gigante, V. Guadalupi, M. Maio, L. Milesi, F. Nole, G. Scagliotti, Giampaolo Tortora, S. Fukasawa, T. Harabayashi, N. Kamiya, T. Kawahara, M. Kawakita, N. Matsubara, K. Matsumoto, K. Nishimura, T. Rikiya, N. Shimizu, T. Tagaki, T. W. Kang, J. H. Kim, S. Kim, H. J. Lee, Y. -G. Lee, S. Y. Rha, H. K. Seo, M. Los, B. Zurawski, P. Cortes, C. Faustino, N. S. Vau, R. da Luz, V. Atduev, D. Kirtbaya, E. Kopyltsov, A. Lykov, U. Marat, S. Orlov, K. Penkov, A. Pirmagomedov, A. Semenov, S. Varlamov, G. Anguera, M. Domenech, R. Girones, A. Gonzalez del Alba, N. L. Milagro, R. Luque, E. M. Ortega, B. Mellado, M. J. Mendez Vidal, E. N. Fernandez, B. P. Valderrama, A. P. Marin, C. Santander, Y. -H. Huang, W. -P. Su, H. -C. Wu, W. Wu, K. -J. Yu, A. Bilici, E. Goker, M. Gumus, A. Karaoglu, U. Kefeli, F. Kose, M. Ozguroglu, D. Tural, H. Turk, S. Yalcin, I. Bondarenko, G. Khareba, Y. Kidik, O. Lychkovskyy, V. Sakalo, S. Shevnia, E. Stakhovskyy, A. Bahl, S. Crabb, T. Powles, P. Sankey, M. Sarwar, P. Benedetto, E. Burgess, N. Dawson, G. Doshi, M. Fleming, J. Maly, M. Parikh, D. Waterhouse

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

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.
Lingua originaleEnglish
pagine (da-a)107-117
Numero di pagine11
RivistaAnnals of Oncology
Volume35
DOI
Stato di pubblicazionePubblicato - 2024

Keywords

  • FGFR
  • erdafitinib
  • metastatic urothelial cancer
  • overall survival
  • pembrolizumab
  • safety

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