When patients with cancer undergo new treatments, temporary cessation of those treatments may help reduce toxicity without affecting efficacy. A recent study compared a conventional continuation strategy to a tyrosine kinase inhibitor (TKI) drug-free interval strategy to determine which is more effective for the first-line treatment of advanced clear cell renal cell carcinoma (RCC).
The open-label, noninferiority, randomized, controlled, phase 2/3 trial was conducted at 60 hospitals throughout the United Kingdom. Patients enrolled in the study were 18 years of age or older with histologically confirmed clear cell RCC; inoperable loco-regional or metastatic disease; no previous systemic therapy for advanced disease; unidimensional, Response Evaluation Criteria in Solid Tumors-defined measurable disease; and an Eastern Cooperative Oncology Group performance status of 0-1.
Patients were screened for eligibility between January 2012 and September 2017. During that time, 920 patients were chosen and randomly assigned 1:1 at baseline to receive either a conventional continuation strategy (n=461) or a drug-free interval strategy (n=459). Each patient adhered to a standard dosing schedule of oral sunitinib (50 mg/day) or oral pazopanib (800 mg/day) for 24 weeks before moving into their randomly allocated group.
Patients in the drug-free interval strategy group were given a treatment break until disease progression occurred, and then treatment was reinstated. Patients in the conventional continuation strategy group continued their treatment without a break. The median follow-up time was 58 months in both the intention-to-treat (ITT) population and the per-protocol population. After week 24, 488 patients were continuing the trial.
The coprimary end points of the study were overall survival and quality-adjusted life years (QALYs). Noninferiority was shown if the lower limit of the 2-sided 95% CI for the overall survival hazard ratio was 0.812 or higher and if the lower limit of the 2-sided 95% CI of the marginal difference in mean QALYs was –0.156 or higher. Noninferiority was seen in the ITT population and was demonstrated for QALYs in the ITT and per-protocol groups.
Hypertension, hepatotoxicity, and fatigue were the most common grade 3 or worse adverse events. A total of 192 patients experienced a serious adverse reaction, and 12 treatment-related deaths occurred.
Noninferiority between both groups could not be concluded; however, no clinically meaningful reduction in life expectancy was seen in either strategy group.
The study authors concluded that treatment breaks can potentially serve as a feasible and cost-effective option to provide lifestyle benefits for patients with RCC during TKI therapy.
