A subset of patients with metastatic renal cell carcinoma (mRCC), deemed as primary refractory, shows progressive disease as the best response to first-line therapy even when treated with novel immune-based combos.
We aimed to assess the outcome of patients treated with second-line cabozantinib for mRCC primary refractory to first-line therapy defined as Response Evaluation Criteria in Solid Tumors (RECIST) progression in the computed tomography scan as the best response to the upfront treatment.
We retrospectively collected data from 11 worldwide centers.
Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan-Meier curves. Cox proportional models were used at univariate and multivariate analyses.
We collected data from 108 patients with mRCC primary refractory to pembrolizumab plus axitinib (17%), nivolumab plus ipilimumab (36%), or tyrosine kinase inhibitors (TKIs; 31% sunitinib and 16% pazopanib). The median OS with cabozantinib was 9.11 mo, and it was 8.84 and 9.11 mo in patients primary refractory to immunocombinations and TKIs, respectively (p = 0.952). A significant difference was found between patients primary refractory to pembrolizumab plus axitinib (OS not reached) and those primary refractory to nivolumab plus ipilimumab (median OS 8.12 mo, p = 0.024). The median PFS with cabozantinib was 7.30 mo, without significant differences between patients primary refractory to immunocombinations and those primary refractory to TKIs (6.90 vs 7.59 mo, p = 0.435) or between patients primary refractory to pembrolizumab plus axitinib and those primary refractory to nivolumab plus ipilimumab (7.92 and 6.02, p = 0.509). Investigator-assessed overall response rates were 21% and 12% in patients primary refractory to first-line immunocombinations and TKIs, respectively, with a clinical benefit of 48% in the overall population.
Our data show that cabozantinib is active in primary refractory mRCC patients regardless of which treatment is received as first-line therapy. Systemic options and prognosis of primary refractory patients with mRCC, particularly those treated with novel immune-based combos, are among the major challenges that we need to face in this field.
Patients primary refractory to first-line therapy are characterized by a poor prognosis. Herein, we aimed to assess the outcome of patients treated with second-line cabozantinib for metastatic renal cell carcinoma (mRCC) primary refractory to first-line therapy. Our results suggest that cabozantinib is active in primary refractory mRCC patients.
European urology focus. 2022 Feb 19 [Epub ahead of print]
Matteo Santoni, Francesco Massari, Sergio Bracarda, Enrique Grande, Marc R Matrana, Mimma Rizzo, Ugo De Giorgi, Umberto Basso, Gaetano Aurilio, Lorena Incorvaia, Angelo Martignetti, Javier Molina-Cerrillo, Veronica Mollica, Alessandro Rizzo, Nicola Battelli
Oncology Unit, Macerata Hospital, Macerata, Italy., Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italia. Electronic address: ., Azienda Ospedaliera Santa Maria, Terni, Italy., Department of Medical Oncology, MD Anderson Cancer Center Madrid, Madrid, Spain., Department of Internal Medicine, Hematology/Oncology, Ochsner Medical Center, New Orleans, LA, USA., A.O.U. Consorziale Policlinico di Bari, Bari, 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 and Neck Tumours, IEO, European Institute of Oncology IRCCS, Milan, Italy., Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy., Dipartimento Oncologico, USL Sud-Est Toscana-Area Senese, Poggibonsi, Italy., Medical Oncology Departmentat, Hospital Ramón y Cajal, Madrid, Spain., Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italia.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/35193819