Efficacy and safety of cabozantinib rechallenge in metastatic renal cell carcinoma: A retrospective multicentric study.

BACKGROUND

Despite metastatic renal cell carcinoma (mRCC) expanded treatment options, disease progression ultimately occurs for most patients. Rechallenge may be a compelling strategy in a refractory setting. Cabozantinib is the standard of care in first and later lines of therapy, but its activity in rechallenge is unknown.

METHODS

This retrospective study assessed the efficacy and safety of cabozantinib rechallenge, as defined by a second exposure after an interval of ≥3 months without treatment or ≥1 other treatment line, in patients with mRCC. The primary endpoint was median progression-free survival (PFS) at rechallenge. Secondary endpoints included overall survival, objective response rate, and safety at rechallenge.

RESULTS

We included 51 mRCC patients who received cabozantinib in a rechallenge setting between 2017 and 2022. Median age at diagnosis was 54 years, 78% were male, 90% had clear cell mRCC, and 92% had prior nephrectomy. 15 patients (29%) were rechallenged after a pause in treatment, whereas 36 (70.6%) had ≥1 other treatment lines between first cabozantinib exposure (CABO-1) and rechallenge (CABO-2). Median PFS was 15.1 months (mo, 95% Confidence interval 11.2-22.1) at CABO-1 and 14.4mo (95%CI 9.8-NR) at CABO-2. Median overall survival was 67.6mo for CABO-1 (95% CI 52.2-NR) and 27.4mo for CABO-2 (95%CI 17.2-NR); objective response rate was 70.6% for CABO-1 and 60% for CABO-2. CABO-2 PFS was higher for patients with CABO-1 PFS > 12 months, and for those who discontinued CABO-1 because of toxicity, without statistical significance. There were no unexpected adverse events.

CONCLUSIONS

Cabozantinib rechallenge is a feasible treatment option with potential clinical benefit for mRCC patients.

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Laurence Albiges received funding from Amgen, Astellas-Pharma, AstraZeneca, Bristol Myers Squibb, Exelixis, Ipsen, Merck KGaA, MSD, Novartis, Pfizer and Roche. Natacha Naoun received funding from Merck. Edouard Auclin is on the advisory boards of Amgen and Sanofi. Philippe Barthélémy is on the advisory boards of Bristol. Myers Squibb, Ipsen, Janssen, MSD, Novartis, Pfizer and Roche, and received honoraria from Astellas, EUSA Pharma and Sanofi. Lionnel Geoffrois received honoraria from Bristol Myers Squibb, Ipsen, Pfizer, Janssen, Merck Serono and MSD. Constance Thibault received funding from Amgen, AstraZeneca, Bristol Myers Squibb, Sanofi, Ipsen, Pfizer, Merck, Janssen, Astellas, MSD. Manon de Vries received funding from AAA, Pfizer, Ipsen, Bristol Myers Squibb. Delphine Borchiellini received research funding from Astellas, AstraZeneca, AVEO, Bayer, Bristol-Myers Squibb, Exelixis, Infinity Pharmaceuticals, Roche, Taiho Oncology, and other funding from Ipsen, Janssen, Pfizer. Lucia Carril-Ajuria received funding from Ipsen. Emeline Colomba received honoraria from Bristol-Myers Squibb, GlaxoSmithKline, Ipsen, Merck and Pfizer. Alice Bernard-Tessier received honoraria from Astellas, Bayer, and funding from Bayer and Orion Clinical. Ronan Flippot received honoraria from Bayer, Astellas, Janssen, Ipsen, Pfizer, MSD and Bristol Myers Squibb. Bernard Escudier received funding from Aveo, Bristol Myers Squibb, Ipsen, Novartis, Pfizer and Roche. Denis Maillet, Carolina Saldana, Laure Hirsch, Charles Vauchier and Edwige Baudry declare no conflict of interest relating to the submitted work.