ASCO GU 2022: Association of Cabozantinib Dose Reductions for Toxicity With Clinical Effectiveness in mRCC: Results From the Canadian Kidney Cancer Information System

(UroToday.com) The 2022 GU ASCO Annual meeting included a renal cell carcinoma (RCC) session highlighting work from Dr. Jeffrey Graham and investigators presenting results assessing the association of cabozantinib dose reductions for toxicity with clinical effectiveness in metastatic RCC. Cabozantinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) with activity in metastatic RCC. TKI toxicity, an indicator of adequate drug exposure, has been associated with clinical effectiveness for sunitinib, pazopanib, and axitinib. The need for dose reductions or dose interruptions for toxicity has also been associated with statistically significant improvements in objective response, progression, and survival for both sunitinib and pazopanib in phase 3 RCTs. Dr. Graham explored whether cabozantinib dose reductions (a surrogate for toxicity) were associated with improved clinical outcomes in metastatic RCC.

Using the Canadian Kidney Cancer Information System database, an analysis was performed of patients treated with cabozantinib in the second-line or later between 2011-2021. The cohort was divided into those needing a dose reduction (defined as less than the starting dose at time of treatment discontinuation) and those who did not (no-dose reduction). Outcomes were compared by dose reduction status, including objective response rate (ORR), time to treatment failure, and overall survival (OS).

There were 260 patients identified who received cabozantinib with the following baseline characteristics: 

ASCOGU22_Graham_0 

 

Among these 260 patients, 103 (39.6%) needed a dose reduction. Across all lines, the ORR was similar between the dose reduction and non-dose reduction groups: 19.6% vs. 18.9% (p = 0.903) respectively. The median time to treatment failure was 12.8 months (95% CI 10.4 – 17.6) in the dose reduction group vs. 6.4 months (95% CI 5.5 – 8.7) in the no-dose reduction group:

 

ASCOGU22_Graham_1 

 

After adjusting for IMDC risk, the hazard ratio for time to treatment failure comparing dose reduction vs. no-dose reduction was 0.69 (95% CI 0.50 - 0.97). The median OS was 29.6 months (95% CI 19.6 – 42.6) in the dose reduction group vs. 15.3 (95% CI 11.0 – 22.6) in the no-dose reduction group:

 

ASCOGU22_Graham_2 

 

After adjusting for IMDC risk, the HR for OS comparing dose reduction vs. no-dose reduction was 0.65 (95% CI 0.43 - 0.98, p = 0.04).

Dr. Graham concluded his presentation of assessing the association of cabozantinib dose reductions for toxicity with clinical effectiveness in metastatic RCC with the following concluding statements:

  • Cabozantinib dose reductions, a surrogate for toxicity and adequate drug exposure, appear to be associated with improved time to treatment failure and OS in metastatic RCC
  • In this cohort, 40% of patients required a dose reduction of cabozantinib, indication that this is a relatively common practice in the real-world setting
  • In contrast to the association of dose reduction and overall survival, there was no apparent difference in ORR
  • Toxicity driven/individualized dosing strategies for cabozantinib alone and in combination with immunotherapy, warrant further investigation

 

Presented By: Jeffrey Graham, MD, University of Manitoba, Winnipeg, MB, Canada

Co-Authors: Naveen S. Basappa, Sunita Ghosh, Hanbo Zhang, Aaron Richard Hansen, Aly-Khan A. Lalani, Daniel Yick Chin Heng, Denis Soulieres, Vincent Castonguay, Christian K. Kollmannsberger, Michel Pavic, Lori Wood, Anil Kapoor, Georg A. Bjarnason

Affiliations: Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada, Cross Cancer Institute/University of Alberta, Edmonton, AB, Canada, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, Department of Oncology, Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada, Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada, Département Hématologie-Oncologie, Centre Hospitalier de l'Université de Montréal, CHU de Quebec-L'Hotel-Dieu de Quebec, Quebec, QC, Canada, Department of Medicine, British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada, Centre Hospitalier Universitaire de Sherbrooke (CRCHUS), Sherbrooke, QC, Canada, Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS, Canada, Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada, Sunnybrook Research Institute, Toronto, ON, Canada

Written By: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022

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