Erdafitinib in patients with advanced solid tumours with FGFR alterations (RAGNAR): an international, single-arm, phase 2 study - 02/08/23
, Martin Schuler, ProfMD b, Gopa Iyer, MD c, Olaf Witt, ProfMD d, Toshihiko Doi, MD e, Shukui Qin, MD f, Josep Tabernero, MD g, David A Reardon, MD h, Christophe Massard, MD i, Anna Minchom, MD j, Iwona Lugowska, MD k, Omar Carranza, PhD l, Dirk Arnold, MD m, Martin Gutierrez, MD n, Helen Winter, DPhil o, Kim Stuyckens, MSc p, Lauren Crow, PhD q, Saltanat Najmi, MS q, Constance Hammond, BS q, Shibu Thomas, PhD q, Ademi Santiago-Walker, PhD q, Spyros Triantos, MD q, Hussein Sweiti, MD q, Yohann Loriot, MD r, ⁎ on behalf of the
RAGNAR Investigators*
Summary |
Background |
FGFR alterations are reported across various malignancies and might act as oncogenic drivers in multiple histologies. Erdafitinib is an oral, selective pan-FGFR tyrosine kinase inhibitor with activity in FGFR-altered advanced urothelial carcinoma. We aimed to evaluate the safety and activity of erdafitinib in previously treated patients with FGFR-altered advanced solid tumours.
Methods |
The single-arm, phase 2 RAGNAR study was conducted at 156 investigative centres (hospitals or oncology practices that are qualified oncology study centres) across 15 countries. The study consisted of four cohorts based on tumour histology and patient age; the results reported in this Article are for the primary cohort of the study, defined as the Broad Panel Cohort, which was histology-agnostic. We recruited patients aged 12 years or older with advanced or metastatic tumours of any histology (except urothelial cancer) with predefined FGFR1–4 alterations (mutations or fusions according to local or central testing). Eligible patients had disease progression on at least one previous line of systemic therapy and no alternative standard therapy available to them, and an Eastern Cooperative Oncology Group performance status of 0–1 (or equivalent for adolescents aged 12–17 years). Patients received once-daily oral erdafitinib (8 mg/day with provision for pharmacodynamically guided up-titration to 9 mg/day) on a continuous 21-day cycle until disease progression or intolerable toxicity. The primary endpoint was objective response rate by independent review committee according to Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1, or Response Assessment In Neuro-Oncology (RANO). The primary analysis was conducted on the treated population of the Broad Panel Cohort. This ongoing study is registered with ClinicalTrials.gov, number NCT04083976.
Findings |
Patients were recruited between Dec 5, 2019, and Feb 15, 2022. Of 217 patients treated with erdafitinib, 97 (45%) patients were female and 120 (55%) were male. The data cutoff was Aug 15, 2022. At a median follow-up of 17·9 months (IQR 13·6–23·9), an objective response was observed in 64 (30% [95% CI 24–36]) of 217 patients across 16 distinct tumour types. The most common grade 3 or higher treatment-emergent adverse events related to erdafitinib were stomatitis (25 [12%]), palmar-plantar erythrodysaesthesia syndrome (12 [6%]), and hyperphosphataemia (11 [5%]). The most commonly occurring serious treatment-related adverse events (grade 3 or higher) were stomatitis in four (2%) patients and diarrhoea in two (1%). There were no treatment-related deaths.
Interpretation |
RAGNAR results show clinical benefit for erdafitinib in the tumour-agnostic setting in patients with advanced solid tumours with susceptible FGFR alterations who have exhausted other treatment options. These results support the continued development of FGFR inhibitors in patients with advanced solid tumours.
Funding |
Janssen Research & Development.
Le texte complet de cet article est disponible en PDF.Plan
Vol 24 - N° 8
P. 925-935 - août 2023 Retour au numéro
Article précédent
- Fractionated initial infusion and booster dose of ARI0002h, a humanised, BCMA-directed CAR T-cell therapy, for patients with relapsed or refractory multiple myeloma (CARTBCMA-HCB-01): a single-arm, multicentre, academic pilot study
- Aina Oliver-Caldés, Verónica González-Calle, Valentín Cabañas, Marta Español-Rego, Paula Rodríguez-Otero, Juan Luis Reguera, Lucía López-Corral, Beatriz Martin-Antonio, Aintzane Zabaleta, Susana Inogés, Sara Varea, Laura Rosiñol, Ascensión López-Díaz de Cerio, Natalia Tovar, Raquel Jiménez, Miriam López-Parra, Luis Gerardo Rodríguez-Lobato, Andrés Sánchez-Salinas, Eulàlia Olesti, Maria Calvo-Orteu, Julio Delgado, José Antonio Pérez-Simón, Bruno Paiva, Felipe Prósper, Joaquín Sáez-Peñataro, Manel Juan, José M Moraleda, María-Victoria Mateos, Mariona Pascal, Alvaro Urbano-Ispizua, Carlos Fernández de Larrea
- Artificial intelligence-supported screen reading versus standard double reading in the Mammography Screening with Artificial Intelligence trial (MASAI): a clinical safety analysis of a randomised, controlled, non-inferiority, single-blinded, screening accuracy study
- Kristina Lång, Viktoria Josefsson, Anna-Maria Larsson, Stefan Larsson, Charlotte Högberg, Hanna Sartor, Solveig Hofvind, Ingvar Andersson, Aldana Rosso
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?