Mir et al found that regorafenib (Stivarga) was active in patients with advanced nonadipocytic soft-tissue sarcoma previously treated with an anthracycline, according to a French-Austrian phase II trial reported in The Lancet Oncology. Regorafenib, a kinase inhibitor, should be evaluated further in this setting, the investigators concluded. Nicolas Penel, MD, of Centre Oscar Lambret, Lille, France, is the corresponding author of The Lancet Oncology article.
In this double-blind trial, 182 patients aged ≥ 18 years who had received anthracycline treatment were randomized to receive regorafenib or placebo in 1 of 4 cohorts: liposarcoma (regorafenib = 20 vs placebo = 23), leiomyosarcoma (28 vs 28), synovial sarcoma (13 vs 14), and other sarcomas (29 vs 27); they were included in the final analysis. Treatment consisted of oral regorafenib at 160 mg/d for 3 weeks on/1 week off or matched placebo. Patients receiving placebo were offered crossover for centrally confirmed disease progression.
The primary endpoint was Response Evaluation Criteria in Solid Tumors (RECIST)-based progression-free survival on central radiologic review in the intention-to-treat population. The study is still open for recruitment to an additional stratum (patients previously treated with pazopanib [Votrient]).
Progression-Free Survival Outcomes and Toxicity
At the cutoff date (January 2016), median progression-free survival was 1.1 months with regorafenib vs 1.7 months with placebo (hazard ratio [HR] = 0.89, P = .70) in the liposarcoma group; 3.7 vs 1.8 months (HR = 0.46, P = .0045) in the leiomyosarcoma group; 5.6 vs 1.0 months (HR = 0.10, P < .0001) in the synovial sarcoma group; and 2.9 vs 1.0 months (HR = 0.46, P = .0061) in the “other sarcoma” group.
The most common clinically significant adverse events of grade ≥ 3 in the regorafenib group prior to placebo patient crossover were arterial hypertension (19% vs 2%), hand and foot skin reaction (15% vs 0%), and asthenia (13% vs 6%). One treatment-related death, due to liver failure, occurred in a patient receiving regorafenib.
The investigators concluded: Regorafenib has an important clinical antitumour effect in non-adipocytic soft tissue sarcomas, improving progression-free survival. Regorafenib should be further evaluated in this setting, and its therapeutic role has to be defined in the context of the growing therapeutic armamentarium, already including one approved multikinase inhibitor, pazopanib.”
The study was funded by Bayer HealthCare. ■
Mir O, et al: Lancet Oncol 17:1732-1742, 2016.