Effect of adding sirolimus (s) to imatinib (im) on tumor response following secondary resistance to im in advanced chordoma.

10541 Background: IM is active in advanced chordoma, possibly by targeting PDGFRB. Secondary progressions following response have been observed. The evidence of AKT activation in a small group of chordoma patients (pts) prompted us to combine an mTOR inhibitor-sirolimus-to IM in IM-resistant advanced chordoma.,Since July 2007, 7 progressive advanced chordoma patients (F=4, M=3; mean age 53 yrs; PS 0-2) with a secondary resistance to IM and biochemical evidence of AKT expression and activation, have started IM 400 mg/day + sirolimus (2-3 mg/day) on an individual use basis. Sirolimus blood levels were evaluated every 2 weeks. 2 pts were biopsed after 3 months of treatment.,Six pts are still on treatment, while one stopped therapy after 3 months for progression. 4 pts are evaluable for response (3 pts too early for response assessment). Treatment was in general well tolerated. The most common side effect requiring treatment discontinuation was G3 leucopenia, with one case of concomitant pneumonia and one case of G3 mucositis. In all cases, pts recovered after stopping treatment. After 4-6 weeks, 3 pts had a PET response (SUV max decrease ≥25%), with subjective improvement and stable disease confirmed on CT/MRI after 3 months of treatment. In one pt, an ulcerated lesion shrunk in a few weeks. Post- treatment AKT assessment in pts undergoing biopsy is under evaluation.,In 3 out of 4 evaluable advanced chordoma pts progressing on IM, tumor response was re-established by adding sirolimus to IM. [Table: see text].