The authors powered the study to detect an improvement in PFS of 14 months (n=99), with 90% power and 2-sided alpha of 0.05. Patients were started at 50mg/day for 28 days with treatment breaks reduced to 7 days instead of the typical 14 days. If grade 2 toxicity developed before day 28, the patients remained on 50 mg for the next cycle with the number of days on treatment individualized aiming for ≤ grade 2 toxicity. Subsequently, the dose was reduced to 37.5 mg and then 25 mg if patients did not tolerate a 50 mg or 37.5 mg dose, respectively, for at least 7 days. On the contrary, patients with minimum toxicity on day 28 were escalated to 62.5 mg and then 75 mg. There were 117 patients enrolled across 12 centers of which 9 patients were removed from the study early due to toxicity (n=5), non-compliance (n=2), and clinical deterioration (n=2). Among the remaining 108 patients, 31.5% were IMDC favorable risk, 58.3% were intermediate, and 10.2% were poor risk. There were 19% of patients with bone metastasis and 83% had previously undergone a nephrectomy. There were 20 patients (18.5%) escalated to 62.5 mg (12 patients) and then to 75 mg (8 patients). Among 49 patients eligible for dose reduction based on standard criteria, a 50 mg dose was maintained for 7-24 days, while 7 patients stayed on the 28-day schedule. The sunitinib dose was reduced to 37.5 mg in 22 patients and to 25 mg in 10 patients. Treatment was stopped in 9.3% of patients secondary to toxicity, which was lower than previous clinical trials (15-19%). Compared to the 4/2 arm of the EFFECT trial, the current study had improved PFS (11.9 months). Furthermore, there were more patients with partial response (47% vs 32%) and complete + partial response (50% vs 32%) compared to the EFFECT trial.
In summary, the authors concluded that individual dosing was safe and superior to PFS outcomes reported in previous clinical trials. One dose does not appear to ‘fit all’, and among patients tolerating sunitinib therapy, dose escalation appears to improve clinical and survival outcomes.
Clinical trial: NCT01499121
Presented By: Georg A. Bjarnason, Sunnybrook Research Institute, Toronto, ON, Canada
Co-Authors: Jennifer J. Knox, Christian K. Kollmannsberger, Denis Soulieres, D. Scott Ernst, Pawel Zalewski, Christina M. Canil, Eric Winquist, Sebastien J. Hotte, Scott A. North, Daniel Yick Chin Heng, Robyn Jane Macfarlane, Peter M. Venner, Anil Kapoor, Aaron Richard Hansen, Bernhard J. Eigl, Piotr Czaykowski, Ben Boyd, Lisa Wang, Naveen S. Basappa
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA