Targeting MET alterations with savolitinib appears to be a better strategy than sunitinib for patients with MET-driven papillary renal cell carcinoma, according to results of the open-label, randomized, phase III SAVOIR trial.1 Patients with MET-driven metastatic papillary renal cell carcinoma treated with savolitinib had numerically longer progression-free survival, overall survival, and objective response rate compared with sunitinib. The results were simultaneously published in JAMA.2
Although 254 patients were screened, only 60 patients were enrolled; 14 of them (23%) were female. Among randomized patients, 12% of the savolitinib group and 37% of the sunitinib group were women.
The authors explained that the low number of randomized patients was due to the trial being halted early since a concurrent study on molecular outcomes suggested that MET alterations did not appear to be a negative predictive factor for treatment outcomes on sunitinib.
“These results, with limited efficacy data, favor savolitinib over sunitinib, and savolitinib showed a superior safety and tolerability profile.”— Toni Choueiri, MD
Tweet this quote
Median progression-free survival was 7 months for savolitinib vs 5.6 months for sunitinib, but the difference was not statistically significant. At data cutoff, 9 (27%) patients in the savolitinib group died vs 13 (48%) in the sunitinib group. Median overall survival was not reached in the savolitinib group vs 13.2 months for sunitinib. Objective response rate was 27% vs 7%, respectively. Median duration of response could not be calculated at the early time point of analysis.
The rate of grade ≥ 3 adverse events was 42% in the savolitinib group vs 81% with sunitinib. Dose modifications were needed in 30% of cases vs 74% with sunitinib. Subsequent anticancer therapies were given after discontinuation of study treatment to 36% of the savolitinib group and 19% of those in the sunitinib group.
“These results, with limited efficacy data, favor savolitinib over sunitinib, and savolitinib showed a superior safety and tolerability profile. Although the retrospective molecular study suggested that MET-driven status did not appear to be a negative predictive factor for treatment outcomes, our clinical findings suggest differently and thus, given the potential to improve treatment for MET-driven papillary renal cell carcinoma with savolitinib, a new study in the same population is under consideration,” said lead author Toni Choueiri, MD, Dana-Farber Cancer Institute, Boston. “Further investigation of savolitinib is warranted.”
Disclosure: SAVOIR was funded by AstraZeneca. Dr. Choueiri has equity ownership or stock options in Pionyr and Tempest; has consulted or advised for Pfizer, Bristol-Myers Squibb, Merck, Novartis/GlaxoSmithKline, Exelixis/Ipsen, Eisai, Roche/Genentech, EMD Serono/Pfizer, Lilly Oncology, Peloton Therapeutics, Heron Therapeutics; and has received grant/research/clinical trial support from AstraZeneca, BMS, Pfizer, Exelixis, Roche, Eisai, Peloton, Merck, Novartis, GSK, and Bayer.
References
1. Choueiri TK, Heng DYC, Lee JL, et al. SAVOIR: A phase III study of savolitinib versus sunitinib in patients with MET-driven papillary renal cell carcinoma. ASCO20 Virtual Scientific Program. Abstract 5002.
2. Choueiri TK, Heng DYC, Lee JL, et al. Efficacy of savolitinib vs sunitinib in patients with MET-driven papillary renal cell carcinoma: The SAVOIR phase 3 randomized clinical trial. JAMA Oncol. May 29, 2020 (early release online).
