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.
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.
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.
Cabozantinib rechallenge is a feasible treatment option with potential clinical benefit for mRCC patients.
European journal of cancer (Oxford, England : 1990). 2023 Aug 18 [Epub ahead of print]
Edwige Baudry, Natacha Naoun, Edouard Auclin, Carolina Saldana, Philippe Barthelemy, Lionnel Geoffrois, Constance Thibault, Manon de Vries-Brilland, Delphine Borchiellini, Denis Maillet, Laure Hirsch, Charles Vauchier, Lucia Carril-Ajuria, Emeline Colomba, Alice Bernard-Tessier, Bernard Escudier, Ronan Flippot, Laurence Albigès
Gustave Roussy, Department of Cancer Medicine, Université Paris-Saclay, Villejuif, France; Institut de Cancérologie de Lorraine, Department of Medical Oncology, Université de Lorraine, Nancy 54000, France., Gustave Roussy, Department of Cancer Medicine, Université Paris-Saclay, Villejuif, France., Hôpital Européen Georges Pompidou, Institut du Cancer Paris CARPEM, AP-HP Centre, Department of Medical Oncology, Université Paris Cité, Paris 75015, France., Hôpital Henri Mondor, AP-HP, Department of Medical Oncology, Université de Paris, Créteil 94000, France., Institut de Cancérologie Strasbourg Europe, Department of Medical Oncology, Strasbourg 67200, France., Institut de Cancérologie de Lorraine, Department of Medical Oncology, Université de Lorraine, Nancy 54000, France., Institut de Cancérologie de l'Ouest, Department of Medical Oncology, Université d'Angers, Angers 49055, France., Centre Antoine-Lacassagne, Department of Medical Oncology, Université Côte d'Azur, Nice 06100, France., Hôpital Lyon-Sud, Université de Lyon, Department of Medical Oncology, Pierre-Bénite 69495, France; Faculté de médecine Jacques Lisfranc, Saint Etienne 42270, France., Hôpital Cochin-Port Royal, Department of Medical Oncology, AP-HP, Paris 75014, France., Hôpital Bichat, AP-HP, Department of Thoracic Oncology, Université de Paris, Paris 75018, France., Gustave Roussy, Department of Cancer Medicine, Université Paris-Saclay, Villejuif, France; CHU Saint Pierre/CHU Brugmann, Brussels, Belgium., Gustave Roussy, Department of Cancer Medicine, Université Paris-Saclay, Villejuif, France. Electronic address: .