Journal article
Cabozantinib in advanced non-clear-cell renal cell carcinoma: a multicentre, retrospective, cohort study
The lancet oncology, Vol.20(4), pp.581-590
04/01/2019
DOI: 10.1016/S1470-2045(18)30907-0
PMCID: PMC6849381
PMID: 30827746
Abstract
Background Cabozantinib is approved for patients with metastatic renal cell carcinoma on the basis of studies done in clear-cell histology. The activity of cabozantinib in patients with non-clear-cell renal cell carcinoma is poorly characterised. We sought to analyse the antitumour activity and toxicity of cabozantinib in advanced non-clear-cell renal cell carcinoma.
Methods We did a multicentre, international, retrospective cohort study of patients with metastatic non-clear-cell renal cell carcinoma treated with oral cabozantinib during any treatment line at 22 centres: 21 in the USA and one in Belgium. Eligibility required patients with histologically confirmed non-clear-cell renal cell carcinoma who received cabozantinib for metastatic disease during any treatment line roughly between 2015 and 2018. Mixed tumours with a clear-cell histology component were excluded. No other restrictive inclusion criteria were applied. Data were obtained from retrospective chart review by investigators at each institution. Demographic, surgical, pathological, and systemic therapy data were captured with uniform database templates to ensure consistent data collection. The main objectives were to estimate the proportion of patients who achieved an objective response, time to treatment failure, and overall survival after treatment.
Findings Of 112 identified patients with non-clear-cell renal cell carcinoma treated at the participating centres, 66 (59%) had papillary histology, 17 (15%) had Xp11.2 translocation histology, 15 (13%) had unclassified histology, ten (9%) had chromophobe histology, and four (4%) had collecting duct histology. The proportion of patients who achieved an objective response across all histologies was 30 (27%, 95% CI 19-36) of 112 patients. At a median follow-up of 11 months (IQR 6-18), median time to treatment failure was 6.7 months (95% CI 5.5-8.6), median progression-free survival was 7.0 months (5.7-9.0), and median overall survival was 12.0 months (9.2-17.0). The most common adverse events of any grade were fatigue (58 [52%]), and diarrhoea (38 [34%]). The most common grade 3 events were skin toxicity (rash and palmar-plantar erythrodysesthesia; five [4%]) and hypertension (four [4%]). No treatment-related deaths were observed. Across 54 patients with available next-generation sequencing data, the most frequently altered somatic genes were CDKN2A (12 [22%]) and MET (11 [20%]) with responses seen irrespective of mutational status.
Interpretation While we await results from prospective studies, this real-world study provides evidence supporting the antitumour activity and safety of cabozantinib across non-clear-cell renal cell carcinomas. Continued support of international collaborations and prospective ongoing studies targeting non-clear-cell renal cell carcinoma subtypes and specific molecular alterations are warranted to improve outcomes across these rare diseases with few evidence-based treatment options. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
Details
- Title: Subtitle
- Cabozantinib in advanced non-clear-cell renal cell carcinoma: a multicentre, retrospective, cohort study
- Creators
- Nieves Martinez Changa - Dana-Farber Cancer InstituteWanling Xie - Dana-Farber Cancer InstituteMehrnet Asim Bilen - Emory UniversityHannah Dzimitrowicz - Duke Medical CenterJarred Burkart - The Ohio State UniversityDaniel M. Geynisman - Fox Chase Cancer CenterArchana Balakrishnan - The Barbara Ann Karmanos Cancer InstituteI. Alex Bowman - The University of Texas Southwestern Medical CenterRohit Jain - Roswell Park Cancer InstituteWalter Stadler - University of ChicagoYousef Zakharia - University of IowaVivek Narayan - Sidney Kimmel Cancer CenterBenoit Beuselinck - Universitair Ziekenhuis LeuvenRana R. McKay - University of California San DiegoAbhishek Tripathi - Oklahoma State University Oklahoma CityRussell Pachynski - Washington University in St. LouisAndrew W. Hahn - Huntsman Cancer InstituteJoAnn Hsu - City Of Hope National Medical CenterSumit A. Shah - Palo Alto InstituteElaine T. Lam - University of Colorado Cancer CenterTracy L. Rose - University of North Carolina at Chapel HillAnthony E. Mega - Brown UniversityNicholas Vogelzang - Comprehensive Cancer Centers of NevadaMichael R. Harrison - Duke Medical CenterAmir Mortazavi - The Ohio State UniversityElizabeth R. Plimack - Fox Chase Cancer CenterUlka Vaishampayan - The Barbara Ann Karmanos Cancer InstituteHans Hammers - The University of Texas Southwestern Medical CenterSaby George - Roswell Park Cancer InstituteNaomi Haas - Sidney Kimmel Cancer CenterNeeraj Agarwal - Huntsman Cancer InstituteSumanta K. Pal - City Of Hope National Medical CenterSandy Srinivas - Palo Alto InstituteBenedito A. Carneiro - Brown UniversityDaniel Y. C. Heng - Baker HughesDominick Bosse - Ottawa HospitalToni K. Choueiri - Dana-Farber Cancer InstituteLauren C. Harshman - Dana-Farber Cancer Institute
- Resource Type
- Journal article
- Publication Details
- The lancet oncology, Vol.20(4), pp.581-590
- DOI
- 10.1016/S1470-2045(18)30907-0
- PMID
- 30827746
- PMCID
- PMC6849381
- NLM abbreviation
- Lancet Oncol
- ISSN
- 1470-2045
- eISSN
- 1474-5488
- Publisher
- Elsevier
- Number of pages
- 10
- Grant note
- P30CA022453 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30 CA086862; P30 CA022453 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 04/01/2019
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984548265102771
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