ASCO GU 2018: A Randomized Phase II Trial of Pazopanib versus Temsirolimus in Patients with Advanced Clear-cell Renal Cell Carcinoma (the TemPa trial)
In 2011, Dr. Tannir and colleagues launched the TemPa trial, a randomized phase II trial of Paz vs. Tem in mRCC patients with intermediate- and poor-risk features in order to determine the optimal treatment agent for these patients. Eligibility required no prior VEGF/mTOR therapy, >=3 MSKCC risk criteria, PS <=2. The primary endpoint was progression free survival (PFS), with secondary endpoints of OS, ORR, and safety.
In December 2017, the trial was closed to further accrual after presentation of the CABOSUN and CheckMate data, which demonstrated impressive ORRs for newer agents. Target accrual was 90 patients, of which 69 were accrued before study closure.
With regard to PFS, there was an interaction between treatment arm and IMDC risk grouping, but there was no difference in PFS between the two agents (mPFS Paz 5.2mo, mPFS Tem 2.6mo, p = 0.16). The ORR% appeared to be higher in Paz (25.7%) than Tem (6.1%), which appeared to maintain the same trend in IMDC intermediate-risk patients. There was no significant differences in mOS between the two agents (mOS Paz 12mo, mOS Tem 7.3mo). There were no significantly different adverse events between the two agents, and no deaths were reported on study.
The findings from this study indicate that neither of these agents is ideally fit for use in intermediate-risk and poor-risk patients now that we have more effective agents such as nivolumab + ipilimumab. We did see that Paz had a significantly longer PFS than Tem in intermediate-risk patients, but this difference may not be clinically meaningful at this point. In particular, neither agent was particularly effective in poor-risk patients. It is important to note the comparative effectiveness of Paz vs. Tem, though, which may have utility in the treatment of some intermediate-risk patients. However, with newer immunomodulatory agents and multi-kinase inhibitors such as cabozantinib, these findings must now take a backseat to more effective agents.
Presented by: Nizar M. Tannir, MD, FACP, MD Anderson Cancer Center
Written by: Shreyas Joshi, MD, Fox Chase Cancer Center, Philadelphia, PA at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA