Results of a prospective phase 2 study of pazopanib in patients with surgically unresectable or metastatic chondrosarcoma

Abstract

Background This single‐arm, multicenter, phase 2 study evaluated the safety and antitumor activity of pazopanib in patients with unresectable or metastatic conventional chondrosarcoma. Methods Eligible patients had conventional chondrosarcoma of any grade with measurable tumors that were unresectable or metastatic. Patients with mesenchymal, dedifferentiated, and extraskeletal myxoid chondrosarcoma subtypes and patients who received prior tyrosine kinase inhibitor therapy were excluded. Pazopanib at 800 mg once daily was administered for 28‐day cycles. Tumor responses were evaluated by local radiology assessments every 2 cycles. The primary endpoint was the disease control rate (DCR) at week 16 (4 cycles). Results Forty‐seven patients were enrolled. The DCR at 16 weeks was 43% (95% confidence interval [CI], 28%‐58%), which was superior to the null hypothesis rate of 30%, but the 2‐sided P value (exact test) was .09 (1‐sided P = .045). One patient had a partial response. The median overall survival was 17.6 months (95% CI, 11.3‐35.0 months), and the median progression‐free survival was 7.9 months (95% CI, 3.7‐12.6 months). Grade 3 or higher adverse events were infrequent; hypertension (26%) and elevated alanine aminotransferase (9%) were most common. Conclusions This study provides evidence of positive drug activity for pazopanib in conventional chondrosarcoma.

<p>Apatinib for Treatment of Inoperable Metastatic or Locally Advanced Chondrosarcoma: What We Can Learn About the Biological Behavior of Chondrosarcoma from a Two-Center Study</p>

“…Because of the diversity of these two subtypes' features, the DCR at 16 weeks was 43% in conventional central CS, and 12-month PFS in extraskeletal myxoid CS reached 74%. 13,14 In our study, the majority of patients had conventional CS (n=20) with an ORR of 15% and median PFS of 7.0 months, which represented a meaningful outcome and supported apatinib treatment in this group of traditionally chemotherapy-resistant disease. Regarding other CS subtypes, although response rates were diverse, [11][12][13][14]16,24,29 longer PFS was observed comparing to other studies.…”

“…[8][9][10] In addition, vascularization increases with increasing histological grade. 10 Imatinib, 11 dasatinib, 12 pazopanib, [13][14][15] ramucirumab, 15 and regorafenib 16 have all been explored in CS of the advanced stage with diverse results. Apatinib is an active anti-angiogenesis tyrosine kinase inhibitor (TKI), which more selectively inhibits vascular endothelial growth factor receptor 2 with an IC 50 of 0.001 μM in vitro while synchronously inhibiting c-kit (0.429 μM), PDGFR-α (>1 μM), Ret (0.013 μM), c-src (0.53 μM), EGFR (>10 μM), HER2 (>10 μM), and FGFR1 (>10 μM).…”

Extraskeletal Myxoid Chondrosarcoma: State of the Art and Current Research on Biology and Clinical Management

“…To the best of our knowledge, no data are available on the efficacy of gemcitabine. Besides cytotoxics, antiangiogenic agents represent a promising alternative systemic treatment, with an antitumor effect that is superior to that seen in the majority of other STSs [ 39 , 40 , 42 , 60 , 61 , 62 ].…”

Mechanical forces switch blood vessel subtypes to arrest adolescent bone growth

“…Our finding that inducible Dmp1 deletion led to increased vessel activity also in subchondral bone suggests that extracellular DMP1 may protect articular cartilage from vessel invasion, which accompanies neoinnervation of the tissue and sensation of pain in osteoarthritis patients [37][38] . Moreover, DMP1-mediated inhibition of angiogenesis in bone may be useful in arresting growth of tumours including osteo-and chondrosarcomas [39][40][41] .…”