Bradley A McGregor1, Aly-Khan A Lalani2, Wanling Xie3, John A Steinharter1, Ziad E Bakouny1, Dylan J Martini4, Justin H Fleischer1, Sarah Abou-Alaiwi1, Amin Nassar1, Pier V Nuzzo5, Marina D Kaymakcalan6, David A Braun1, Xiao X Wei1, Lauren C Harshman1, Mehmet A Bilen4, Toni K Choueiri7. 1. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston MA, USA. 2. Department of Oncology, Juravinski Cancer Centre, McMaster University, Hamilton ON, Canada. 3. Department of Data Sciences, Dana-Farber Cancer Institute, Boston MA, USA. 4. Winship Cancer Institute of Emory University, Atlanta GA, USA. 5. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston MA, USA; Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genoa, Genoa, Italy. 6. Department of Pharmacy and Clinical Support, Dana-Farber Cancer Institute, Boston, MA, USA. 7. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston MA, USA. Electronic address: Toni_Choueiri@dfci.harvard.edu.
Abstract
BACKGROUND: Cabozantinib is approved for the first and subsequent line treatment of metastatic clear-cell renal cell carcinoma (ccRCC) based on trials in which most patients were immune checkpoint blockade (ICB) naive. With an expanding role of ICB in earlier lines of therapy, we assessed activity of cabozantinib in patients with metastatic ccRCC after progressing on anti-PD-1/PD-L1-based ICBs. METHODS: We retrospectively analysed the clinical outcomes of 86 patients from 2 academic centres who received cabozantinib after progression on ICB alone, ICB in combination with vascular endothelial growth factor inhibitors (VEGFis) or ICB in combination with other therapies. Overall response rate (ORR, investigator assessed), time to treatment failure (TTF), overall survival (OS) and toxicities leading to dose reductions or cessation were evaluated. RESULTS: Eighty-six patients were included in the analysis; the median age was 63 years (range 33-84) and the median number of prior therapies was 2 (range 1-10). The type of prior ICB therapy was ICBs alone (64%), an ICB in combination with a VEGFi (29%) or ICBs in combination with other therapies (7%). At the time of cabozantinib treatment, 71% of patients were in the International Metastatic RCC Database Consortium good- or intermediate-risk groups. Approximately half of patients (52%) were started on cabozantinib at the full 60 mg daily dose. The ORR was 36% (95% confidence interval [CI] = 26-47%) with no complete response and 43% achieving stable disease; 21% had primary progressive disease. The median TTF was 6.5 months (95% CI = 5.3-8.5.). The median OS was 13.1 months (95% CI = 8.7-NR) with 55% (95% CI = 41-66%) OS rate at 12 months. Most common reasons for dose reductions were fatigue (27%), palmar-plantar erythrodysesthesia (16%) and diarrhoea (10%). CONCLUSIONS: Cabozantinib is active in patients treated with prior ICB-based therapies, with no new safety signals. This study supports the use of cabozantinib after ICB-based therapies.
BACKGROUND:Cabozantinib is approved for the first and subsequent line treatment of metastatic clear-cell renal cell carcinoma (ccRCC) based on trials in which most patients were immune checkpoint blockade (ICB) naive. With an expanding role of ICB in earlier lines of therapy, we assessed activity of cabozantinib in patients with metastatic ccRCC after progressing on anti-PD-1/PD-L1-based ICBs. METHODS: We retrospectively analysed the clinical outcomes of 86 patients from 2 academic centres who received cabozantinib after progression on ICB alone, ICB in combination with vascular endothelial growth factor inhibitors (VEGFis) or ICB in combination with other therapies. Overall response rate (ORR, investigator assessed), time to treatment failure (TTF), overall survival (OS) and toxicities leading to dose reductions or cessation were evaluated. RESULTS: Eighty-six patients were included in the analysis; the median age was 63 years (range 33-84) and the median number of prior therapies was 2 (range 1-10). The type of prior ICB therapy was ICBs alone (64%), an ICB in combination with a VEGFi (29%) or ICBs in combination with other therapies (7%). At the time of cabozantinib treatment, 71% of patients were in the International Metastatic RCC Database Consortium good- or intermediate-risk groups. Approximately half of patients (52%) were started on cabozantinib at the full 60 mg daily dose. The ORR was 36% (95% confidence interval [CI] = 26-47%) with no complete response and 43% achieving stable disease; 21% had primary progressive disease. The median TTF was 6.5 months (95% CI = 5.3-8.5.). The median OS was 13.1 months (95% CI = 8.7-NR) with 55% (95% CI = 41-66%) OS rate at 12 months. Most common reasons for dose reductions were fatigue (27%), palmar-plantar erythrodysesthesia (16%) and diarrhoea (10%). CONCLUSIONS:Cabozantinib is active in patients treated with prior ICB-based therapies, with no new safety signals. This study supports the use of cabozantinib after ICB-based therapies.
Authors: Pablo Maroto; Camillo Porta; Jaume Capdevila; Andrea B Apolo; Santiago Viteri; Cristina Rodriguez-Antona; Lidia Martin; Daniel Castellano Journal: Ther Adv Med Oncol Date: 2022-07-13 Impact factor: 5.485
Authors: E Grande; T Alonso-Gordoa; O Reig; E Esteban; D Castellano; X Garcia-Del-Muro; M J Mendez; J García-Donas; M González Rodríguez; J A Arranz-Arija; P Lopez-Criado; J Molina-Cerrillo; B Mellado; C Alvarez-Fernandez; G De Velasco; M A Cuéllar-Rivas; R M Rodríguez-Alonso; J F Rodríguez-Moreno; C Suarez-Rodriguez Journal: ESMO Open Date: 2022-04-08
Authors: Hui-Wen Lue; Daniel S Derrick; Soumya Rao; Ahna Van Gaest; Larry Cheng; Jennifer Podolak; Samantha Lawson; Changhui Xue; Devin Garg; Ralph White; Christopher W Ryan; Justin M Drake; Anna Ritz; Laura M Heiser; George V Thomas Journal: Cell Rep Med Date: 2021-05-07