Activity of cabozantinib after immune checkpoint blockade in metastatic clear-cell renal cell carcinoma
| Autor: | Toni K. Choueiri, Amin Nassar, Pier Vitale Nuzzo, Marina D. Kaymakcalan, David A. Braun, Mehmet Asim Bilen, Sarah Abou-Alaiwi, Dylan J. Martini, John A. Steinharter, Ziad Bakouny, Justin H. Fleischer, Aly-Khan A. Lalani, Xiao X. Wei, Wanling Xie, Bradley Alexander McGregor, Lauren C. Harshman |
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| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology Cancer Research medicine.medical_specialty Georgia Time Factors Cabozantinib Pyridines medicine.medical_treatment Angiogenesis Inhibitors 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Renal cell carcinoma Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Anilides Carcinoma Renal Cell Immune Checkpoint Inhibitors Protein Kinase Inhibitors Aged Retrospective Studies Aged 80 and over business.industry Immunotherapy Middle Aged medicine.disease Kidney Neoplasms Confidence interval Immune checkpoint Blockade Vascular endothelial growth factor Clear cell renal cell carcinoma Treatment Outcome 030104 developmental biology chemistry 030220 oncology & carcinogenesis Female business Boston |
| Zdroj: | European Journal of Cancer. 135:203-210 |
| ISSN: | 0959-8049 |
| DOI: | 10.1016/j.ejca.2020.05.009 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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