Abstract
BackgroundPatients with advanced chordoma are often treated with tyrosine kinase inhibitors without any predictive factor to guide decision. We report herein an ancillary analysis of the the Angionext phase II trial (NCT 00874874).ResultsFrom May 2011 to January 2014, 26 were sampled. The 9-month PFS rate was 72.9% (95%-CI: 45.9-87.9). During sorafenib treatment, a significant increase in PlGF (18.4 vs 43.8 pg/mL, p<0.001) was noted along with a non-significant increase in VEGF (0.7 vs 1.0 ng/mL, p=0.07). VEGF at D1 >1.04 ng/mL (HR=12.5, 95%-CI: 1.37-114, p=0.025) and VEGF at D7 >1.36 ng/mL (HR=10.7, 95%-CI: 1.16-98, p=0.037) were associated with shorter PFS. The 9-month PFS rate was 92.3% (95%-CI: 56.6-98.9) when VEGF at D1 was ≤1.04 ng/mL versus 23.3% (95%-CI: 1.0-63.2) when >1.04 ng/mL.Patients and MethodsChordoma patients were treated with sorafenib 800 mg/day for 9 months, unless earlier occurrence of progression or toxicities. Six biomarkers (sE-Selectin, VEGF, VEGF-C, placental growth factor (PlGF), Thrombospondin, Stem Cell Factor (SCF)) were measured at baseline (day 1: D1) and day 7 (D7).ConclusionHigh levels of VEGF was associated with poor outcome.
Highlights
Chordomas are rare primary bone tumors with an incidence lower than 1 case per millions of inhabitants and peak of incidence between 50 and 60 years old [1].They are derived from undifferentiated notochordal remnants, and the cornerstone of treatment remains surgery with large enbloc-resection, possible in less than 50% of cases, given the necessary neurological sacrifice and the devastating surgical procedure
VEGF at D1 >1.04 ng/mL (HR=12.5, 95%CI: 1.37-114, p=0.025) and VEGF at day 7 (D7) >1.36 ng/mL (HR=10.7, 95%-CI: 1.16-98, p=0.037) were associated with shorter progression-free survival (PFS)
High levels of VEGF was associated with poor outcome
Summary
Chordomas are rare primary bone tumors with an incidence lower than 1 case per millions of inhabitants and peak of incidence between 50 and 60 years old [1]. They are derived from undifferentiated notochordal remnants (skull base, mobile spine and sacrum), and the cornerstone of treatment remains surgery with large enbloc-resection, possible in less than 50% of cases, given the necessary neurological sacrifice and the devastating surgical procedure. There is no standard systemic therapy: conventional chemotherapy is regarded as an inappropriate option [1]; molecularly targeted therapies, imatinib, are often used in first line, despite a low level of evidence based on several phase II trials [5]. We report an ancillary analysis of the the Angionext phase II trial (NCT 00874874)
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