Jacques Raphael1, Alia Thawer2, Georg A Bjarnason3. 1. Sunnybrook Health Sciences Centre, Division of Medical Oncology, Department of Medicine, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada. Electronic address: raphaeljack13@hotmail.com. 2. Sunnybrook Health Sciences Centre, Department of Pharmacy, Toronto, ON, Canada. 3. Sunnybrook Health Sciences Centre, Division of Medical Oncology, Department of Medicine, Toronto, ON, Canada.
Abstract
PURPOSE: Previous pharmacologic studies demonstrated that higher sunitinib exposure is associated with improved clinical outcomes in patients with metastatic renal cell carcinoma (mRCC). We aimed to assess the efficacy and toxicity of sunitinib dose-escalation in mRCC patients progressing on the standard 50mg dose. METHODS: A single-institution retrospective review was conducted on mRCC patients, treated outside trials with a 50mg sunitinib dose given on an individualized schedule between October 2009 and January 2016, who subsequently progressed on imaging. All progressing patients who were dose-escalated to 62.5 and 75mg on an individualized schedule if toxicity permitted were eligible for this analysis. Median progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. PFS1 and 2 were defined as the time between the start of sunitinib and first progression and the time between dose-escalation and second progression respectively. RESULTS: A total of 25 eligible patients were identified with a median follow-up of 40.3 months (Q1-Q3: 11.1-66.6) and a mean age of 54 years (standard deviation: 12.4). Most of the patients underwent cytoreductive surgery (92%) and were men (88%). In total 32%, 44%, and 24% had a good, intermediate, and poor prognostic Heng Score, respectively. At standard doses, 60% and 16% of patients had a partial response (PR) and a stable disease (SD) as best response respectively for a median duration of 11.4 months (95% CI: 3-20.7). A total of 6 patients (24%) had progressive disease as best response. After progression, 36% and 28% had PR and SD on higher doses of sunitinib respectively for a median duration of 7.8 months (95% CI: 6.3-12.4). The median PFS1, PFS2 and OS were 6.1 months (95% CI: 2.3-19.4), 6.7 months (95% CI: 3.1-8.4) and 63.7 months (95% CI: 26-NR) respectively. The most common adverse events after dose-escalation were fatigue (56%), diarrhea (40%) and skin toxicity (28%). CONCLUSION: Patients with mRCC who progress on 50mg sunitinib dose, may derive a clinical benefit and prolonged survival from dose-escalation with acceptable toxicity profiles. These results need to be confirmed in prospective studies with the aim to overcome drug resistance and delay the change in systemic therapy at progression.
PURPOSE: Previous pharmacologic studies demonstrated that higher sunitinib exposure is associated with improved clinical outcomes in patients with metastatic renal cell carcinoma (mRCC). We aimed to assess the efficacy and toxicity of sunitinib dose-escalation in mRCC patients progressing on the standard 50mg dose. METHODS: A single-institution retrospective review was conducted on mRCC patients, treated outside trials with a 50mg sunitinib dose given on an individualized schedule between October 2009 and January 2016, who subsequently progressed on imaging. All progressing patients who were dose-escalated to 62.5 and 75mg on an individualized schedule if toxicity permitted were eligible for this analysis. Median progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. PFS1 and 2 were defined as the time between the start of sunitinib and first progression and the time between dose-escalation and second progression respectively. RESULTS: A total of 25 eligible patients were identified with a median follow-up of 40.3 months (Q1-Q3: 11.1-66.6) and a mean age of 54 years (standard deviation: 12.4). Most of the patients underwent cytoreductive surgery (92%) and were men (88%). In total 32%, 44%, and 24% had a good, intermediate, and poor prognostic Heng Score, respectively. At standard doses, 60% and 16% of patients had a partial response (PR) and a stable disease (SD) as best response respectively for a median duration of 11.4 months (95% CI: 3-20.7). A total of 6 patients (24%) had progressive disease as best response. After progression, 36% and 28% had PR and SD on higher doses of sunitinib respectively for a median duration of 7.8 months (95% CI: 6.3-12.4). The median PFS1, PFS2 and OS were 6.1 months (95% CI: 2.3-19.4), 6.7 months (95% CI: 3.1-8.4) and 63.7 months (95% CI: 26-NR) respectively. The most common adverse events after dose-escalation were fatigue (56%), diarrhea (40%) and skin toxicity (28%). CONCLUSION:Patients with mRCC who progress on 50mg sunitinib dose, may derive a clinical benefit and prolonged survival from dose-escalation with acceptable toxicity profiles. These results need to be confirmed in prospective studies with the aim to overcome drug resistance and delay the change in systemic therapy at progression.
Authors: Pierre I Karakiewicz; Emanuele Zaffuto; Anil Kapoor; Naveen S Basappa; Georg A Bjarnason; Normand Blais; Rodney H Breau; Christina Canil; Darrel Drachenberg; Sebastien J Hotte; Claudio Jeldres; Michael A S Jewett; Wassim Kassouf; Christian Kollmannsberger; Luke T Lavallée; Ranjena Maloni; Francois Patenaude; Frédéric Pouliot; M Neil Reaume; Robert Sabbagh; Bobby Shayegan; Alan So; Denis Soulières; Simon Tanguay; Lori Wood; Marco Bandini Journal: Can Urol Assoc J Date: 2018-06 Impact factor: 1.862
Authors: Stefanie D Krens; Nielka P van Erp; Stefanie L Groenland; Dirk Jan A R Moes; Sasja F Mulder; Ingrid M E Desar; Tom van der Hulle; Neeltje Steeghs; Carla M L van Herpen Journal: BMC Cancer Date: 2022-03-02 Impact factor: 4.430