Pazopanib in Advanced Extraskeletal Myxoid Chondrosarcoma
Findings from a cohort of a phase II study reported by Stacchiotti et al in The Lancet Oncology indicated activity of the antiangiogenic agent pazopanib in advanced extraskeletal myxoid chondrosarcoma. As noted by the investigators, this rare sarcoma has low sensitivity to cytotoxic chemotherapy, with some evidence suggesting that antiangiogenic agents may be more active.
Study Details
The study includes three cohorts of patients with different histotypes of advanced sarcomas; findings in the typical solitary fibrous tumor and malignant-dedifferentiated solitary fibrous tumor cohorts are to be reported separately.
The extraskeletal myxoid chondrosarcoma cohort included 23 eligible patients with NR4A3-translocated metastatic or unresectable disease with progression in the previous 6 months from 11 sites in Europe. Patients were treated between June 2014 and January 2017 with oral pazopanib at 800 mg/d continuously until disease progression or unacceptable toxicity. The primary endpoint was objective response.
Responses
Median follow-up was 27 months. One patient died (due to cardiopulmonary failure unrelated to treatment) before the primary analysis, leaving 22 evaluable for efficacy. Objective response on Response Evaluation Criteria in Solid Tumors, version 1.1, was observed in 4 patients (18%, all partial responses), with an additional 16 patients (73%) having stable disease.
All 4 patients with objective responses were among the 19 patients with an EWSR1-NR4A3 fusion (21% response rate). Radiologic tumor shrinkage was observed in 12 patients (55%). Median progression-free survival was not reached in patients with tumor shrinkage, compared with 7.7 months in 10 patients with no evidence of shrinkage (P < .0001).
Adverse Events
Among all 26 patients receiving at least one dose of study drug, the most common grade 3 adverse events were hypertension (35%), increased alanine aminotransferase (23%), and increased aspartate aminotransferase (19%). Leukopenia—all grade 1 or 2—was the most common hematologic toxicity, occurring in 50% of patients. A grade 3 hematologic adverse event (anemia) occurred in one patient. No grade 4 events were reported. Adverse events led to treatment discontinuation in one patient. No treatment-related deaths were observed.
The investigators concluded, “Pazopanib had clinically meaningful antitumour activity in patients with progressive and advanced extraskeletal myxoid chondrosarcoma and could be considered a suitable option after failure to respond to first-line anthracycline-based chemotherapy in these patients.”
Silvia Stacchiotti, MD, of Fondazione IRCCS Istituto Nazionale Tumori, Milan, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the Spanish Group for Research on Sarcomas, Italian Sarcoma Group, French Sarcoma Group, GlaxoSmithKline, and Novartis. For full disclosures of the study authors, visit thelancet.com.
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