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
Copyright © 2023 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:35 |
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| Enthalten in: |
Annals of oncology : official journal of the European Society for Medical Oncology - 35(2024), 1 vom: 15. Jan., Seite 107-117 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Siefker-Radtke, A O [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.01.2024 Date Revised 15.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.annonc.2023.10.003 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM363639918 |
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| 100 | 1 | |a Siefker-Radtke, A O |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Erdafitinib versus pembrolizumab in pretreated patients with advanced or metastatic urothelial cancer with select FGFR alterations |b cohort 2 of the randomized phase III THOR trial |
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| 500 | |a Date Revised 15.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
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| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a FGFR | |
| 650 | 4 | |a erdafitinib | |
| 650 | 4 | |a metastatic urothelial cancer | |
| 650 | 4 | |a overall survival | |
| 650 | 4 | |a pembrolizumab | |
| 650 | 4 | |a safety | |
| 650 | 7 | |a pembrolizumab |2 NLM | |
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| 650 | 7 | |a erdafitinib |2 NLM | |
| 650 | 7 | |a 890E37NHMV |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 650 | 7 | |a Pyrazoles |2 NLM | |
| 650 | 7 | |a Quinoxalines |2 NLM | |
| 700 | 1 | |a Matsubara, N |e verfasserin |4 aut | |
| 700 | 1 | |a Park, S H |e verfasserin |4 aut | |
| 700 | 1 | |a Huddart, R A |e verfasserin |4 aut | |
| 700 | 1 | |a Burgess, E F |e verfasserin |4 aut | |
| 700 | 1 | |a Özgüroğlu, M |e verfasserin |4 aut | |
| 700 | 1 | |a Valderrama, B P |e verfasserin |4 aut | |
| 700 | 1 | |a Laguerre, B |e verfasserin |4 aut | |
| 700 | 1 | |a Basso, U |e verfasserin |4 aut | |
| 700 | 1 | |a Triantos, S |e verfasserin |4 aut | |
| 700 | 1 | |a Akapame, S |e verfasserin |4 aut | |
| 700 | 1 | |a Kean, Y |e verfasserin |4 aut | |
| 700 | 1 | |a Deprince, K |e verfasserin |4 aut | |
| 700 | 1 | |a Mukhopadhyay, S |e verfasserin |4 aut | |
| 700 | 1 | |a Loriot, Y |e verfasserin |4 aut | |
| 700 | 0 | |a THOR cohort 2 investigators |e verfasserin |4 aut | |
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| 700 | 1 | |a Sewak, Sanjeev |e investigator |4 oth | |
| 700 | 1 | |a Tran, Ben |e investigator |4 oth | |
| 700 | 1 | |a Pichler, Martin |e investigator |4 oth | |
| 700 | 1 | |a Shariat, Shahrokh |e investigator |4 oth | |
| 700 | 1 | |a Rottey, Sylvie |e investigator |4 oth | |
| 700 | 1 | |a Schatteman, Peter |e investigator |4 oth | |
| 700 | 1 | |a Schrijvers, Dirk |e investigator |4 oth | |
| 700 | 1 | |a Verschaeve, Vincent |e investigator |4 oth | |
| 700 | 1 | |a Vulsteke, Christof |e investigator |4 oth | |
| 700 | 1 | |a Barros Leite Ferreira, Luiza Aleixo |e investigator |4 oth | |
| 700 | 1 | |a de Santana Gomes Andrea Juliana, Pereira |e investigator |4 oth | |
| 700 | 1 | |a Junior, Joao Antonio |e investigator |4 oth | |
| 700 | 1 | |a Azevedo, Sergio |e investigator |4 oth | |
| 700 | 1 | |a Bastos, Diogo |e investigator |4 oth | |
| 700 | 1 | |a Borges, Giuliano |e investigator |4 oth | |
| 700 | 1 | |a Dettino, Aldo |e investigator |4 oth | |
| 700 | 1 | |a Antonio, Pires Luis |e investigator |4 oth | |
| 700 | 1 | |a Luz, Murilo |e investigator |4 oth | |
| 700 | 1 | |a Martins, Suelen |e investigator |4 oth | |
| 700 | 1 | |a Mota, Jose Mauricio |e investigator |4 oth | |
| 700 | 1 | |a Toledo, Joseane |e investigator |4 oth | |
| 700 | 1 | |a Eigl, Bernhard |e investigator |4 oth | |
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| 700 | 1 | |a Pan, Hongming |e investigator |4 oth | |
| 700 | 1 | |a Sun, Zhongquan |e investigator |4 oth | |
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