MET signaling is a key molecular driver in the treatment of papillary renal carcinoma, however, treatment strategies in the metastatic setting are limited
During the 2021 Genitourinary Cancers Symposium, the phase II SWOG 1500 trial (NCT02761057) was presented, which evaluated the efficacy of cabozantinib, crizotinib, or savolitinib versus sunitinib in the treatment of metastatic papillary renal carcinoma (mPRC). Since there is no ideal therapy in the metastatic setting, the aim of this trial was to compare an existing pattern (sunitinib) with the other MET-targeted tyrosine kinase inhibitors.
Eligible patients even received up to previous systemic therapy, excluding anti-VEGF agents. Participants were randomized to the 1:1:1:1 ratio to receive sunitinib 50 mg/day (four weeks yes, two weeks no), cabozantinib 60 mg/day, crizotinib 250 mg/day, or savolitinib 600 mg/day. Patients were stratified by prior therapy and pRC subtype (I versus II versus unspecified). The main objective was to compare progression-free survival (PFS) for each experimental arm versus sunitinib.
With 41 eligible patients per arm, 85% power is calculated to detect a 75% improvement in median PFS with a unilateral alpha of 0.10 using intention-to-treat analysis. A pre-planned futility analysis was performed after the occurrence of 50% of PFS events. Secondary outcomes included toxicity, response rate, and overall survival.
In all, 152 individuals were enrolled between April 2016 and December 2019. The mean age was 66 years and 76% were male; 92% were not exposed to previous systemic therapy. According to the local pathological review, 18%, 54%, and 28% of patients were characterized as having type I, II and “unspecified” histology, respectively. In contrast, the frequency of type I, II and “unspecified” by the central review was 30%, 45%, and 25%, respectively.
The provision for the savolitinib and crizotinib arms was interrupted early due to futility (hazard ratio of PFS > 1.0 for both). Recruitment of participants continued until the completion in the arms of sunitinib and cabozantinib.
The median PFS was significantly higher with cabozantinib compared to sunitinib, being 9.2 versus 5.6 months (HR 0.61; CI 95% 0.37-0.98; p 0.021), respectively.
Grade 3 or 4 adverse events occurred in 69%, 72%, 37%, and 39% of patients who received sunitinib, cabozantinib, crizotinib, and savolitinib, respectively.
The authors conclude that only cabozantinib resulted in a statistically and clinically significant increase in PFS in patients with pRC compared to sunitinib. These data support the use of cabozantinib as a treatment standard for eligible patients with metastatic pRC.
Pal SK, et al. Sunitinib versus cabozantinib, crizotinib or savolitinib in metastatic papillary renal cell carcinoma (pRCC): Results from the randomized phase II SWOG 1500 study. Abstract 270. 2021 Genitourinary Cancers Symposium. DOI:10.1200/JCO.2021.39.6_suppl,270