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Targeted inhibitor induces responses for soft tissue sarcoma
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CHICAGO — The receptor tyrosine kinase inhibitor anlotinib extended PFS and showed greater antitumor activity compared with placebo among patients with soft tissue sarcoma who regressed on or were intolerant to anthracycline-based chemotherapy, according to data presented at the ASCO Annual Meeting
“No standard therapy is available in China for [patients with] soft tissue sarcoma who progressed after first-line chemotherapy,” Yihebali Chi, MD, PhD, of Cancer Institute and Hospital at the Chinese Academy of Medical Sciences in Beijing, said during her presentation. “Anlotinib [Advenchen Laboratories, Jiangsu Chia-Tai Tianqing Pharmaceutical] is a multitarget receptor tyrosine kinase inhibitor that targets VEGFR, FGFR, PDGFR and c-Kit. Previously, anlotinib has shown single-agent activity in a single arm, phase 2 study presented at ASCO in 2016.”
In the phase 3 randomized, double-blind trial of anlotinib, Chi and colleagues assessed 233 Chinese patients with undifferentiated pleomorphic sarcoma, liposarcoma, leiomyosarcoma, synovial sarcoma, alveolar soft part sarcoma, fibrosarcoma, clear cell sarcoma or epithelioid sarcoma.
The researchers randomly assigned patients 2:1 to anlotinib or placebo. Patients receive 12 mg daily anlotinib for 2 weeks on, 1 week off.
PFS served as the study’s primary endpoint. Secondary endpoints included objective response rate, disease control rate and OS.
Patients treated with anlotinib demonstrated a median PFS of 6.27 months (95% CI, 4.3-8.4) compared with 1.47 months (95% CI, 1.43-1.57) for placebo (HR = 0.33; P < .0001).
ORR was 10.13% among those treated with anlotinib compared with 1.33% for placebo (P < .0145). The disease control rate also was higher with anlotinib (55.7% vs. 22.67%; P < .0001).
In a subgroup analysis, patients with synovial sarcoma (n = 57), leiomyosarcoma (n = 41) and alveolar soft part sarcoma (n = 56) all had significant improvements in PFS compared with placebo (P <.0001 for all). However, among patients with undifferentiated pleomorphic sarcoma (n =20), liposarcoma (n = 22), fibrosarcoma (20) and clear cell sarcoma or epithelioid sarcoma (n = 17) the improvements seen with anlotinib did not reach statistical significance.
OS data were not yet mature.
The most common grade 3 or higher adverse events in the anlotinib group included hypertension (18.99%), gamma glutamyl transferase elevation (4.43%), increased triglycerides (4.43%), elevated LDL (3.16%), hyponatremia (3.16%) and reduced neutrophil count (3.16%). – by Cassie Homer
Reference:
Chi Y, et al. Abstract 11503. Presented at ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: The authors report no relevant financial disclosures.
Perspective
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Seth M. Pollack, MD
Soft tissue sarcomas are cancers of the bone and soft-tissue comprising about 1% of all cancers with few options in the advanced/metastatic setting. In the United States, a tyrosine kinase inhibitor name pazopanib (Votrient, Novartis) is FDA approved for the treatment of these tumors but, in China, there are no approved options in the second-line setting for these patients. This was a randomized double-blind trial in China testing a TKI called anlotinib vs. placebo. There are many types of soft tissue sarcoma, and these were all allowed into this trial. One-hundred fifty-eight patients were randomized to anlotinib and 75 to placebo in 2:1 randomization. Anlotinib significantly improved PFS (6.27 vs. 1.5 months). This was true in a number of different types of sarcoma including synovial sarcoma, leiomyosarcoma, alveolar soft part sarcoma and others. The treatment does have toxicities, but is very well tolerated in comparison to the chemotherapies that these patients may be considering as second-line treatments. The most serious toxicity was high blood pressure; this is a common side effect with this class of drugs and can usually be controlled with blood pressure medicine. Studies are already ongoing in the U.S. to confirm the activity of anlotinib and my guess is that these studies will reproduce what was seen in this Chinese study and anlotinib may ultimately be an option for soft tissue sarcoma patients in the U.S.
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