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Response to imatinib plus sirolimus in advanced chordoma

S Stacchiotti1, A Marrari, E Tamborini

  • 1Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. silvia.stacchiotti@istitutotumori.mi.it

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|July 3, 2009
PubMed
Abstract

Insights

Combining imatinib (IM) with sirolimus shows promise for advanced chordoma resistant to IM alone. This mTOR inhibitor combination demonstrated significant clinical benefit and response rates in a small patient cohort.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Imatinib (IM) demonstrates activity in advanced chordoma.
  • Evidence suggests mammalian target of rapamycin (mTOR) pathway activation in resistant chordoma.
  • This study investigates combining an mTOR inhibitor, sirolimus, with IM for IM-resistant advanced chordoma.

Purpose of the Study:

  • To evaluate the efficacy of combining imatinib (IM) with sirolimus in patients with imatinib-resistant advanced chordoma.
  • To assess the impact of mTOR pathway inhibition on treatment response in advanced chordoma.

Main Methods:

  • A cohort of 10 patients with progressive, IM-resistant advanced chordoma received IM (400 mg/day) plus sirolimus (2 mg/day).
  • Patients had biochemical or immunohistochemical evidence of mTOR pathway activation.
  • Response was assessed using RECIST, Choi criteria, and positron emission tomography (PET).

Main Results:

  • The mean treatment duration was 9 months.
  • Using Choi criteria, 7 out of 9 assessable patients achieved a partial response (PR).
  • An 89% clinical benefit rate (CR + PR + SD ≥ 6 months) was observed. Pretreatment mTOR pathway activation was confirmed in all patients.

Conclusions:

  • The mammalian target of rapamycin (mTOR) pathway is activated in chordoma, in addition to PDGFRB.
  • Combining imatinib (IM) with rapalogs (like sirolimus) may be an effective strategy for treating IM-resistant chordomas.
  • Targeting the mTOR pathway offers a potential therapeutic avenue for advanced chordoma.

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