Sunitinib remains effective with shorter dosing schedule in renal cell carcinoma

Eric Jonasch, MD

CHICAGO — Sunitinib administered for 2 weeks followed by 1 week off induced strong response rates in patients with metastatic renal cell carcinoma without an increase in adverse events, according to findings presented at the ASCO Annual Meeting.

Sunitinib (Sutent, Pfizer) — an anti-angiogenic agent — is traditionally administered for 4 weeks followed by 2 weeks off, but “significant toxicities” occur in the third and fourth weeks of therapy, according to Eric Jonasch, MD, professor in the department of genitourinary medical oncology, division of cancer medicine, at The University of Texas MD Anderson Cancer Center, and colleagues. The researchers “hypothesized that a 2-week on, 1-week off schedule would provide improved toxicity without compromising efficacy.”

Jonasch and colleagues enrolled 60 patients and treated 59 (median age, 65.5 years; range, 45-92 years) in the multicenter, single-arm study. The researchers chose this sample size to certify that the upper bound of a 95% confidence would be lower than the standard sunitinib schedule rate of 25% to 30% if the sample rate was 10% to 15%.

Patients received 50 mg sunitinib for 2 weeks followed by 1 week off, with schedule and dose alterations in the event of toxicities greater than grade 3.

The percentage of patients who experienced greater than grade 3 fatigue, diarrhea or hand-foot syndrome served as the primary outcome.

Additional outcomes included response rate, PFS and rate of dose reductions.

Fourteen patients (24%) experienced grade 3 or greater fatigue, diarrhea or hand-foot syndrome (95% CI, 13.6-36.6). Researchers found this comparable to the average of 25% to 30% in the 4 weeks on/2 weeks off dosing schedule for sunitinib. The lower bound of the confidence interval fell in the center of the researchers’ target rate of 10% to 15%.

The most common adverse events potentially related to the study drug included diarrhea (75%; grade 3 events = 5), fatigue (71%; grade 3 events = 6) and hand-foot syndrome (54%; grade 3 events = 3). The response rate was 37% (n = 22; 95% CI, 25-50.9). Patients who had data on secondary endpoints experienced a median PFS of 19.3 months (95% CI, 8.2 months-not reached) and 33 out of 56 patients (59%) experienced a dose reduction.

“Sunitinib administered in a [2 weeks on/1 week off] schedule … did not result in a lower rate of grade 3 or higher fatigue, diarrhea or hand-foot syndrome when compared [with] historical data from trials employing a [4 weeks on/2 weeks off] schedule. However, efficacy data showed a robust response rate and a prolonged PFS, suggestive of long-term tolerability in patients receiving sunitinib on a [2 weeks on/1 week off] schedule,” the researchers wrote. “Evaluation of toxicity kinetics and patient quality of life is ongoing.” – by Julia Ernst, MS

Reference:

Jonasch E, et al. Abstract 4513. Presented at: ASCO Annual Meeting; June 2-6, 2017; Chicago.

Disclosures: Jonasch reports that he is a consultant or adviser for Cerulean Pharma, Eisai, Exelixis, Genentech/Roche, Novartis and Pfizer; receives research funding from Exelixis, Novartis, Onyx and Pfizer; and receives travel, accommodations and expenses from Cerulean Pharma, Novartis and Pfizer. Please see the full study for a list of all other researchers’ relevant financial disclosures.