SAN FRANCISCO—Progression-free survival (PFS) among patients with intermediate-risk advanced clear-cell renal cell carcinoma (aCCRCC) is significantly longer with pazopanib than temsirolimus as first-line therapy, according to the findings of a randomized phase II clinical trial presented at the 2018 Genitourinary Cancers Symposium. Pazopanib therapy also appeared to elicit a better objective response rate (ORR).
Median progression-free survival (PFS), the study’s primary end point, was 5.2 months (95% CI 3.6–7.4) for pazopanib compared with 2.6 months (95% CI 1.9–4.2) for temsirolimus (p = 0.7), Nizar M. Tannir, MD, and colleagues at the University of Texas Health Science Center at Houston reported. Among patients with intermediate-risk disease as defined by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria, pazopanib was associated with a significant 62% decreased risk of progression compared with temsirolimus The median overall survival was 12 months (95% CI 8.3–20.1) for the pazopanib group and 7.4 months (95% CI 5.3–17.4) for the temsirolimus group (p = 0.61). The study found no significant difference between the drugs among patients in the IMDC poor-risk group.
“After adjustment for IMDC grouping, pazopanib yielded a significantly longer PFS than temsirolimus in patients with IMDC intermediate-risk group disease,” Dr Tannir told attendees during a presentation of the study’s findings. “Pazopanib yielded higher objective response rate than temsirolimus, particularly in patients with IMDC intermediate-risk disease.”
The study included 69 treatment-naïve patients (52 male) with a median age of 61 years. Of these, 25 patients (34%) had intermediate-risk disease and 44 (66%) had poor-risk disease. Investigators randomly assigned 35 patients to receive pazopanib (13 intermediate- and 22 poor-risk patients) and 34 to receive temsirolimus (12 intermediate- and 22 poor-risk patients). The pazopanib dosage was 800 mg orally once daily and the temsirolimus dosage was 25 mg intravenously once weekly. Only 2 patients in each study discontinued treatment because of adverse events. Patients were given an opportunity to receive the other agent at disease progression. A blinded radiologist assessed radiographic response using RECIST v1.1 criteria.
For 1 patient, no date of death was available. Fifty-eight (85.3%) of the remaining 68 patients died. Sixty-eight patients were available for evaluation of response. The overall ORR was 26% in pazopanib group compared with 6% in the temsirolimus group (p = 0.046). Among patients with intermediate-risk disease, the ORR was 40% among pazopanib recipients vs 0% for temsirolimus-treated patients. For patients with poor-risk disease, the ORR was 15% and 8.7%, respectively.
Tannir NM, Ross JA, Devine CE, et al. A randomized phase II trial of pazopanib (PAZ) versus temsirolimus (TEM) in patients (pts) with advanced clear-cell renal cell carcinoma (aCCRCC) of intermediate and poor risk (the TemPa trial). Presented at the 2018 Genitourinary Cancers Symposium, held in San Francisco Feb. 8-10. Abstract 583.