In a phase II study reported in the Journal of Clinical Oncology, Moshe C. Ornstein, MD, of Cleveland Clinic Taussig Cancer Institute, and colleagues found that an intermittent schedule of sunitinib (Sutent) may be feasible in patients with previously untreated metastatic renal cell carcinoma.
In the study, 37 patients with clear cell metastatic renal cell carcinoma enrolled between August 2010 and September 2012 were treated with 4 cycles of sunitinib at 50 mg once per day for 4 weeks followed by 2 weeks off treatment. Patients with ≥ 10% reduction in tumor burden after 4 cycles had sunitinib treatment held, with restaging scans performed every 2 cycles.
Sunitinib was restarted for 2 cycles in patients with ≥ 10% increase in tumor burden and held again if the tumor burden was reduced by ≥ 10%. Intermittent dosing was to continue until disease progression on Response Evaluation Criteria in Solid Tumors (RECIST) or unacceptable toxicity.
Among the 37 patients, 20 patients (54%) were eligible for the intermittent-dosing phase. Reasons for ineligibility for intermittent therapy were progressive disease (13 patients), toxicity (1 patients), and consent withdrawal (3 patients) before the end of cycle 4. Among all patients, the median change in tumor burden during the first 4 cycles was a reduction of 1.7 cm (range = –6.1 to 5.2 cm), with partial response occurring in 17 patients (46%). In the 20 patients eligible for intermittent therapy, the median reduction in tumor burden was 2.0 cm (range = –0.7 to –5.2 cm), representing a median 45% decrease (range = 13%–86% decrease).
Outcomes in Intermittent Phase
At data cutoff, 16 of 20 patients entering the intermittent phase had restarted therapy after an initial break, 3 had not reached the tumor growth threshold to restart therapy, and 1 withdrew from the study. Of the 16 patients who restarted therapy, 12 exhibited regression that permitted ≥ 1 subsequent break and 3 developed progressive disease. A total of 83 breaks were taken among all patients, with a median of 3 breaks per patient (range = 1–11).
The median duration of treatment breaks was 8.3 weeks (range = 4.7–192.1 weeks), and the median period of retreatment was 12.0 weeks (range = 2.0–86.9 weeks). Most patients exhibited a “sawtooth pattern” of increase in tumor burden while on break and a decreased burden while on treatment. In seven patients, prolonged breaks of 3.2 to 43.6 months were possible. In five patients meeting criteria for breaks, an overall increasing tumor burden warranted resumption of the standard sunitinib schedule.
At last analysis (in June 2016), median progression-free survival was 22.4 months among all patients and 37.6 months in the 20 patients who entered the intermittent phase. Median overall survival among all patients was 34.8 months.
The investigators concluded: “Periodic extended sunitinib treatment breaks are feasible and clinical efficacy does not seem to be compromised.” ■