Imatinib in advanced chordoma: A retrospective case series analysis

Eur J Cancer. 2015 Nov;51(17):2609-14. doi: 10.1016/j.ejca.2015.07.038. Epub 2015 Aug 14.

Abstract

Introduction: Imatinib showed activity in 50 chordoma patients treated within a Phase II study. In that study, 70% of patients remained with stable disease (SD), median progression free survival (PFS) was 9 months and median overall survival (OS) was 34 months. We now report on a retrospective series of PDGFB/PDGFRB positive advanced chordoma patients treated with imatinib as a single agent within a compassionate-use programme at Istituto Nazionale Tumori, Milan, Italy (INT) between August 2002 and November 2010, when the programme was closed.

Methods: 48 patients were consecutively treated with imatinib 800 mg/d. All patients had inoperable and progressive disease before starting imatinib. Demographics, treatment duration, toxicity and response rate by Response Evaluation Criteria in Solid Tumors (RECIST) were retrospectively recorded.

Results: The median duration of therapy was 7 months (1-46.5). No patient is on therapy at present. 46 patients were evaluable for response. No partial responses were detected. Best response was: stable disease 34 (74%), progressive disease 12 (26%). At a median follow-up of 24.5 months (0.5-117), median PFS was 9.9 months (95% confidence interval (CI) 6.7-13). Eight patients (16.5%) remained on therapy >18 months and 10 patients (21%) remained progression-free >18 months. Median OS was 30 months (95% CI 20-40), with 24 (50%) patients dead at the time of the present analysis.

Conclusions: We confirm the activity of imatinib in locally advanced and metastatic chordoma, in terms of >70% tumour growth arrest in previously progressive patients. Median duration of response lasted almost 10 months, with >20% of patients progression-free at 18+ months.

Keywords: Chemotherapy; Chordoma; Imatinib; Metastasis; Sarcoma; Targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Chordoma / drug therapy*
  • Chordoma / metabolism
  • Chordoma / pathology
  • Compassionate Use Trials*
  • Disease-Free Survival
  • Edema / chemically induced
  • Follow-Up Studies
  • Humans
  • Imatinib Mesylate / adverse effects
  • Imatinib Mesylate / therapeutic use*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Proto-Oncogene Proteins c-sis / metabolism
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-sis
  • Imatinib Mesylate
  • Receptor, Platelet-Derived Growth Factor beta