A phase II trial showed that the multi-target tyrosine kinase inhibitor anlotinib has promising efficacy across a variety of subtypes of advanced refractory soft-tissue sarcoma (STS). The trial was presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago (abstract 11005).
“In China, no standard therapy is available for patients with STS who fail chemotherapy,” said Yihebali Chi, MD, of the Chinese Academy of Medical Sciences in Beijing, who presented the study. A phase I study by her group found a recommended anlotinib dose of 12 mg daily on a 2 weeks on/1 week off schedule.
The phase II study included 166 patients, 154 of whom received at least 2 cycles of treatment. All patients were previously treated with anthracycline-containing chemotherapy; the median age was 44 years, and 60.24% of patients were male. The study included a range of STS subtypes; 28.31% of patients had synovial sarcoma, 15.66% had leiomyosarcoma, and 11.45% had malignant fibrous histiocytoma, among others.
The primary endpoint was progression-free survival (PFS) at 12 weeks, and 57.23% of patients met this criteria. The disease control rate was 73.49%, and the objective response rate (ORR) was 11.45%.
With regard to STS subtypes, several appeared to derive more benefit from anlotinib than others: 69.2% of leiomyosarcoma patients were progression-free at 12 weeks, as were 76.92% of alveolar soft part sarcoma patients; several others also exceeded 60%. The ORR was highest in alveolar soft part sarcoma, at 46.15%.
The median PFS in the study was 5.63 months. It was 11.07 months in leiomyosarcoma patients, and the median was not reached in patients with alveolar soft part sarcoma.
The most common grade 3/4 adverse events included hypertension in 8%, hypertriglyceridemia in 5%, and pneumothorax in 5%. At lower grades, hand-foot reaction, proteinuria, and diarrhea were common. The median treatment duration was 3.53 months; 24 patients (14.46%) needed a dose reduction.
“Anlotinib is effective in different pathologic types of STS,” Chi said, adding that it is particularly promising in alveolar soft part sarcoma. She also noted that pneumothorax is a concerning adverse event. A phase III trial of the drug in this setting is now ongoing.
The discussant for the session, Gary K. Schwartz, MD, of Columbia University School of Medicine in New York, said the phase III study is a reasonable next step for the development of the drug. “If positive, it could represent a treatment option in China for patients with STS who progress after anthracycline-based chemotherapy,” he said, adding that it is not yet possible to make direct comparisons with other therapy options.