Advanced chordoma treated by first-line molecular targeted therapies: Outcomes and prognostic factors. A retrospective study of the French Sarcoma Group (GSF/GETO) and the Association des Neuro-Oncologues d'Expression Française (ANOCEF)

Eur J Cancer. 2017 Jul:79:119-128. doi: 10.1016/j.ejca.2017.03.037. Epub 2017 May 4.

Abstract

Background: To assess the role of first-line Molecular Targeted Therapies (MTTs) in Advanced chordoma (AC) patients.

Methods: Retrospective study of 80 patients treated between January 2004 and December 2015 at 15 major French Sarcoma or Neurooncology Centres.

Results: The sex ratio M/F was 46/34. The median age was 59 (6-86) years. The primary sites were the sacrum (50, 62.5%), mobile spine (12, 15.0%), and skull base (18, 22.5%). Metastases were present in 28 patients (36.0%). The first line of MTTs consisted of imatinib (62, 77.5%), sorafenib (11, 13.7%), erlotinib (5, 6.3%), sunitinib (1, 1.2%) and temsirolimus (1, 1.2%). The reported responses were: partial response (5, 6.3%), stable disease (58, 72.5%), or progressive disease (10, 12.5%). Symptomatic improvement was seen in 28/66 assessable patients (42.4%) and was associated with an objective response occurrence (p = 0.005), imatinib (p = 0.020) or erlotinib use (p = 0.028). The median progression-free survival (PFS) was 9.4°months (95% CI, [6.8-16.1]). Two independent factors of poor prognosis for PFS were identified: a skull-based primary location (HR = 2.5, p = 0.019), and the interval between diagnosis and MTT of <52months (HR = 2.8, p < 0.001). The median overall survival (OS) was 4.4°years (95% CI, [3.8-5.6]). Four independent factors of poor prognosis for OS were identified: the presence of liver metastases (HR = 13.2, p < 0.001), pain requiring opioids (HR = 2.9, p = 0.012), skull-based primary location (HR = 19.7, p < 0.001), and prior radiotherapy (photon alone) (HR = 2.5, p = 0.024). The PFS and OS did not significantly differ between the MTT.

Conclusions: The prognostic factors identified require validation in an independent database but are potently useful to guide treatment decisions and design further clinical trials.

Keywords: Anti-EGFR; Antiangiogenics; Chordoma; Imatinib; Molecular targeted therapy; Prognostic factors.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Child
  • Chordoma / drug therapy*
  • Chordoma / mortality
  • Erlotinib Hydrochloride / therapeutic use*
  • Female
  • France / epidemiology
  • Humans
  • Imatinib Mesylate / therapeutic use*
  • Indoles / therapeutic use
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods*
  • Molecular Targeted Therapy / mortality
  • Niacinamide / analogs & derivatives
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / therapeutic use
  • Pyrroles / therapeutic use
  • Retrospective Studies
  • Sirolimus / analogs & derivatives
  • Sirolimus / therapeutic use
  • Skull Base Neoplasms / drug therapy*
  • Skull Base Neoplasms / mortality
  • Sorafenib
  • Sunitinib
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Indoles
  • Phenylurea Compounds
  • Pyrroles
  • Niacinamide
  • temsirolimus
  • Imatinib Mesylate
  • Sorafenib
  • Erlotinib Hydrochloride
  • Sunitinib
  • Sirolimus