Higher Safety, Efficacy With Savolitinib vs Sunitinib for Papillary RCC

In a study comparing savolitinib with sunitinib for the treatment of patients with papillary renal cell carcinoma (PRCC) savolitinib yielded a higher overall survival (OS) rate with less adverse events (AEs; JAMA Oncol. 2020;6[8]:1247-1255).

“Because some cases of PRCC are MET-driven, MET inhibition could be a targeted treatment approach. In previous studies, savolitinib (AZD6094, HMPL-504, volitinib), a highly selective MET-tyrosine kinase inhibitor, demonstrated antitumor activity in this patient group,” wrote Toni K. Choueiri, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues.

The open-label, phase 3 SAVOIR clinical trial was a multi-center study conducted at 32 centers across 7 countries. Starting in July 2017, a total of 254 adults with MET-driven, metastatic PRCC with 1 or more measurable lesions were screened for inclusion in the trial. Those who had previously received sunitinib or a MET inhibitor were excluded from the study.

At the data cutoff in August 2019, a total of 60 patients remained and were randomized into 2 groups; 33 patients were given savolitinib 600 mg once daily and the other 27 received sunitinib 50 mg once daily for 4 weeks, followed by 2 weeks without treatment (median age, 60 years and 65 years, respectively).

The progression-free survival (PFS, assessed by investigator and confirmed by blinded independent central review) was the primary end point, whereas overall survival (OS), objective response rate (ORR), duration of response, and safety and tolerability were secondary end points.

Study findings showed that most patients had a chromosome 7 gain (savolitinib, 30 [91%]; sunitinib, 26 [96%]) and had received no prior therapy (savolitinib, 28 [85%]; sunitinib, 25 [93%]). Savolitinib yielded a numerically greater PFS, OS, and ORR over sunitinib. However, the median PFS was not statistically different between the groups, with 7.0 months (95% CI, 2.8 to not calculated) for savolitinib and 5.6 months (95% CI, 4.1-6.9) for sunitinib (hazard ratio, 0.71; 95% CI, 0.37-1.36; P = .31).

Grade 3 or higher AEs were reported in 14 (42%) savolitinib recipients and 22 (81%) sunitinib recipients, with AE-related dose modifications made for 10 (30%) and 20 (74%), respectively. Following discontinuation, 12 (36%) and 5 (19%) of patients receiving savolitinib and sunitinib, respectively, were given subsequent anticancer therapy.

“Although patient numbers and follow-up were limited, savolitinib demonstrated encouraging efficacy vs sunitinib, with fewer grade 3 or higher AEs and dose modifications. Further investigation of savolitinib as a treatment option for MET-driven PRCC is warranted,” concluded Dr Choueiri et al.—Alexandra Graziano