A multicenter phase 2 single arm study of cabozantinib in patients with advanced or unresectable renal cell carcinoma pre-treated with one immune-checkpoint inhibitor: The BREAKPOINT trial (Meet-Uro trial 03).

First-line therapies based on immune-checkpoint inhibitors (ICIs) significantly improved survival of metastatic renal cell carcinoma (mRCC) patients. Cabozantinib was shown to target kinases involved in immune-escape and to prolong survival in patients pre-treated with tyrosine-kinase-inhibitors (TKIs). The impact of ICIs combinations in first line on subsequent therapies is still unclear.

This is an open label, multicenter, single arm, phase II study designed to assess activity, safety and efficacy of cabozantinib in mRCC patients progressed after an adjuvant or first line anti-Programmed Death (PD)-1/PD-Ligand (PD-L) 1-based therapy. Primary endpoint was progression free survival (PFS), secondary endpoints were overall survival (OS), objective response rate (ORR) and safety.

31 patients were included in the analysis. After a median (m) follow-up of 11.9 months, mPFS was 8.3 months (90%CI 3.9-17.4) and mOS was 13.8 months (95%CI 7.7-29.0). ORR was 37.9% with an additional 13 patients achieving disease stability. Grade 3-4 adverse events occurred in 47% of patients, including more frequently creatine phosphokinase (CPK) serum level elevation, neutropenia, hyponatremia, diarrhea, hand-food syndrome, oral mucositis and hypertension.

The BREAKPOINT trial met its primary endpoint showing that cabozantinib as second line therapy after ICIs was active in mRCC. Safety profile was manageable.

NCT03463681 - A Study of CaBozantinib in Patients With Advanced or Unresectable Renal cEll cArcinoma (BREAKPOINT) - https://clinicaltrials.gov/ct2/show/NCT03463681.

Tumori. 2022 Nov 29 [Epub ahead of print]

Giuseppe Procopio, Mélanie Claps, Chiara Pircher, Luca Porcu, Pierangela Sepe, Valentina Guadalupi, Ugo De Giorgi, Davide Bimbatti, Franco Nolè, Francesco Carrozza, Sebastiano Buti, Roberto Iacovelli, Chiara Ciccarese, Cristina Masini, Cinzia Baldessari, Laura Doni, Antonio Cusmai, Angela Gernone, Sarah Scagliarini, Sandro Pignata, Filippo de Braud, Elena Verzoni

Medical Oncology Unit, Fondazione IRCSS Istituto Nazionale dei Tumori di Milano, Milan, Italy., Methodology for Clinical Research Laboratory, Oncology Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy., Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy., Department of Medical Oncology, Istituto Oncologico Veneto IOV, IRCCS, Padova, Italy., Medical Oncology Division of Urogenital and Head & Neck Tumours, IEO, European Institute of Oncology IRCCS, Milan., Department of Medical Oncology, AUSL della Romagna, Ospedale Civile degli Infermi, Faenza, Italy., Medical Oncology Unit, University Hospital of Parma, Parma, Italy., Medical Oncology Unit, Comprehensive Cancer Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy., Department of Medical Oncology, Arcispedale Santa Maria Nuova, AUSL-IRCCS di Reggio Emilia, Reggio Emilia, Italy., Medical Oncology, Department of Oncology and Haematology, AOU Policlinico di Modena, Modena, Italy., Department of Oncology, Oncology Unit, University Hospital Careggi, Largo Brambilla, Firenze, Italy., Department of Oncology "Don Tonino Bello", IRCCS "Giovanni Paolo II", Bari, Italy., University Department of Medical Oncology, Azienda Ospedaliera Policlinico, Bari, Italy., Department of Oncology, AORN A. Cardarelli, Naples, Italy., Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale Napoli, Italy.