Regorafenib (multi-kinase/VEGFR TKI) shows numerically longer OS in advanced sarcoma, but crossover-adjusted benefit drives the signal

Regorafenib is an oral multi-kinase inhibitor with anti-angiogenic activity (notably VEGFR) that has been studied across multiple sarcoma subtypes; this pooled OS analysis combined two randomized, double-blind, placebo-controlled Phase 2 programs (REGOSARC; NCT01900743 and the bone-sarcoma platform; NCT02389244) that allowed placebo-to-regorafenib crossover at progression. In the all-comers pooled population (n=355; 91.5% metastatic; median follow-up 70.9 months), median OS was 12.8 months with regorafenib vs 9.5 months with placebo (HR 0.85, 95%CI 0.67-1.06; p=0.148); after statistical adjustment for crossover, the estimated HR shifted to 0.59 (RPSFTM) or 0.62 (MIPE), though with very wide CIs, and a subtype-restricted analysis excluding chordoma/liposarcoma (n=289) was still not conventionally significant (reported ~20% death-risk reduction; p=0.083). Against typical post-chemotherapy metastatic STS benchmarks where later-line systemic options often deliver modest disease control (and where REGOSARC itself primarily improved PFS, not clearly OS), these OS deltas look directionally encouraging but remain hard to interpret because crossover was substantial and the pooled population is histology-mixed (i.e., not a clean “new SOC” comparison in any one subtype).