Friday, May 16, 2008

ASCO, but will you receive?

Online abstracts are now available for the sarcoma presentations scheduled for the American Society of Clinical Oncologists meetings later this month. I spent a few minutes going through them and didn't notice any obviously relevant epithelioid sarcoma stuff buried in the abstracts, but I'm not qualified to make that judgement and it's better to wait until after the meetings to see what gets covered in the medical trade press anyway.

Ariad posted some phase I results for deforolimus that look encouraging for soft-tissue sarcoma generally:

Abstract No:
J Clin Oncol 26: 2008 (May 20 suppl; abstr 3509)
M. M. Mita, C. D. Britten, E. Poplin, W. D. Tap, A. Carmona, L. Yonemoto, D. S. Wages, C. L. Bedrosian, E. H. Rubin, A. W. Tolcher
Background: Deforolimus is a non-pro-drug rapamycin analog which specifically and potently inhibits mTOR. In Trial 202 intravenous deforolimus demonstrated notable anti-tumor activity in bone and soft tissue sarcomas. (JCO 2006; 24, 18S: 9505). Oral deforolimus allows greater treatment flexibility and offers potential to treat patients in a maintenance setting. We report preliminary results on oral deforolimus in a comprehensive dose finding study in patients (pts) with refractory malignancies. Methods: The trial was an open label single arm study with dose escalation and a standard 3+3 design. Patients had advanced/metastatic solid tumors refractory to therapy. 7 regimens, all over a 28 day cycle were investigated. Definitions of dose limiting toxicity (DLT; Gr 4 or Gr 3>3 days) were based on CTC criteria. Anti-tumor activity was evaluated by modified RECIST criteria. Patients achieving stable disease (SD) or better lasting for at least 4 cycles of 28 days were classified as achieving clinical benefit response (CBR). Results: 147 pts (85 sarcoma) received deforolimus. Median age was 56 (range 23-84 years); 65 (44%) pts were male. Pts had a median of 2 cytotoxic therapies at entry (range 0-7); 113 (77%) of this population had documented progressing disease at enrollment. The median ECOG score was 1 (range 0-2). The DLT for all regimens was aphthous-ulcer like mouth sores which were reversible by dose reduction or symptomatic therapy. 36 pts achieved CBRs (23 sarcomas). MTD was increased with the addition of a weekly dose holiday interval. CBRs were seen in all regimens and several types of sarcomas and a variety of carcinomas. 24 pts received 40 mg QDx5/wk and in this group 3 of 13 (23%) sarcomas had CBR; 2 (liposarcoma, dendritic cell sarcoma) (15.4%) achieved PR. Pharmacodynamic analysis showed potent inhibition of mTOR. 7 patients remain on therapy after 6-24 cycles. Conclusions: Oral deforolimus has a safety and anti-tumor activity profile consistent with the intravenous form. 40 mg QDx5 each week is an active, well tolerated regimen and has been selected for further evaluation in SUCCEED, a global phase 3 trial of patients with metastatic soft-tissue and bone sarcoma in the maintenance setting.

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