Patients who have intermediate or poor-risk advanced renal cell carcinoma may see extended progression-free survival and overall survival in a phase II trial comparing pazopanib with temsirolimus, according to a presentation by Nizar M. Tannir, MD, FACP, at the 2018 Genitourinary Cancers Symposium.
Nizar M.Tannir, MD, FACP
Patients who have intermediate or poor-risk advanced renal cell carcinoma (RCC) may see extended progression-free survival (PFS) and overall survival (OS) in a phase II trial comparing pazopanib (Votrient) with temsirolimus (Torisel), according to a presentation by Nizar M. Tannir, MD, FACP, at the 2018 Genitourinary Cancers Symposium. Historically, temsirolimus has shown level 1 evidence in patients with advanced RCC with poor-risk disease. To date, no trial has compared a VEGFR-TKI with temsirolimus as frontline therapy in this disease state.
Tannir and colleagues from The University of Texas MD Anderson Cancer Center randomly assigned treatment-naïve patients with advanced RCC and ≥3 risk factors to receive pazopanib (800 mg) or temsirolimus (25 mg). Ninety patients were randomized at the start of the trial. The patients were treated until disease progression or unacceptable toxicity, at which time patients were given the option of crossing over to receive the other agent after randomization. The primary endpoint for the trial was PFS, and the secondary endpoints were OS, objective response rate (ORR), and safety.
In September 2017, new patient accrual was closed. A total of 69 patients were eligible and evaluable. The researchers reported that the patients had a median age of 61 years. A total of 52 patients were male (75%), with 44 (64%) having poor risk according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. Thirty patients (43%) had undergone prior nephrectomy.
Thirty-five patients received pazopanib (intermediate risk, 13; poor risk, 22) and 34 patients received temsirolimus (intermediate risk, 12; poor risk, 22). Kaplan-Meier analysis was used for PFS and OS, and the Fisher’s exact test was used for comparison of ORR between pazopanib and temsirolimus.
Of the 69 patients, 67 experienced disease progression or died. The median PFS was 5.2 months (95% CI, 3.6-7.4) for patients who received pazopanib and 2.6 months (95% CI, 1.9-4.2) for temsirolimus (P = .16). The hazard ratio (HR) was 0.70 (0.43-1.14).
“There was no significant difference between the 2 arms for the primary endpoint of progression-free survival,” said lead author Tannir during the presentation.
The researchers also assessed the treatment arm versus the IMDC risk group. They found that patients in the intermediate group had a hazard ratio of 0.38 (95% CI, 0.16-0.92; P = .03), favoring pazopanib, and patients in the poor-risk group had an HR of 1.21 (95% CI, 0.65-2.24; P = .54).
“We performed an assessment between the treatment arm and the IMDC risk group. This interaction was significant at P = .04. Within the intermediate-risk group, the HR between pazopanib versus temsirolimus was 0.38 in favor of pazopanib,” said Tannir.
The researchers reported that the median OS was 12.0 months (95% CI, 8.3-20.1) for patients who were administered pazopanib and 7.4 months (95% CI, 5.3-17.4) for patients who received temsirolimus (P = .61). Twenty-six percent (9 of 35 patients) who received pazopanib and 6% (2 of 33) of patients who received temsirolimus had a partial response (P = .046).
The researchers reported that adverse events (AEs) were consistent with the known safety profiles of pazopanib and temsirolimus. Only 2 patients in each arm discontinued treatment due to AEs. Specifically, treatment-emergent AEs reported in the pazopanib arm were (all grades) fatigue (74%), diarrhea (69%), nausea (60%), hypothyroidism (60%), and hypertension (54%). Grade 3/4 AEs were 26%, 3%, 9%, 0%, and 26%, respectively. In the temsirolimus arm, all-grade AEs were fatigue (65%), diarrhea (18%), nausea (29%), and hypertension (12%); no patient developed any-grade hypothyroidism as an AE. Grade 3/4 AEs in the temsirolimus arm were 24%, 0%, 6%, and 6%, respectively. No grade 5 AEs were reported.
Tannir and colleagues concluded that after adjustment for IMDC risk group, pazopanib yielded significantly longer PFS rates than temsirolimus in patients with IMDC intermediate-risk disease. In addition, pazopanib yielded higher ORRs than temsirolimus, particularly in patients with IMDC intermediate-risk disease, and it also yielded numerically longer OS in patients with IMDC intermediate-risk disease. Both agents were ineffective in patients with IMDC poor-risk disease.
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) who have intermediate or poor-risk disease (the TemPa trial). Presented at: 2018 Genitourinary Cancers Symposium. J Clin Oncol. 2018;36(suppl 6S; abstr 583). ascopubs.org/doi/abs/10.1200/JCO.2018.36.6_suppl.583.