A retrospective study from the Royal Marsden Hospital (RMH) of patients with malignant perivascular epithelioid cell tumors (PEComa) receiving treatment with sirolimus (SI) or temsirolimus (TSI).

Abstract

10038 Background: Perivascular epithelioid cell tumors (PEComas) are rare tumors driven by tuberous sclerosis complex gene mutations causing upregulation of mTOR. Two studies reporting a total of five patients (pts) have described the treatment of PEComa by mTOR inhibition. We report the outcome of 7 pts with PEComa treated with SI or TSI at RMH. Methods: A retrospective analysis was performed on all pts with PEComa referred to the Sarcoma unit at RMH between 2000 and 2011. Data collected included gender, performance status, site of primary tumour, tumour size, surgery, SI/TSI and SI/TSI dose, toxicity according to common toxicity criteria (CTC) version 2.0 and response by RECIST. Results: Five (71%) pts were female, median age was 46 years. Two (29%) had metastatic disease at baseline. Most common primary site was the gastrointestinal tract (29%). Six pts received SI, one TSI. Median treatment duration was 131 days (7-1135). TSI was given at 25 mg IV weekly. Median starting dose of SI was 3 mg daily (1-4), median highest dose was 4 mg daily (1-5). Best responses by computed tomography (CT) scan by RECIST criteria were partial response: 3 (43%), stable disease: 2 (29%) and progressive disease (PD): 1 (14%). One pt only received 7 days of SI and was therefore not evaluable. Two pts continue on treatment, 3 stopped due to PD, one stopped due to grade (gr) 3 thrombocytopenia and one due to gr 3 cough, but two weeks later had confirmed PD on CT. Other toxicities reported were generally mild (gr 1/2) and included mucositis (n:3), rash (n:2), fatigue (n:1), anaemia (n:1), tooth pain (n:1) and oedema (n:1). One pt experienced a grade 3 trigeminal nerve pain leading to dose reduction in SI. Therapeutic drug monitoring was not performed. Conclusions: Our study confirms that SI and TSI are well tolerated with good clinical response and supports the continuous administration of SI or TSI for PEComas. A median treatment time of only 131 days indicates that most pts have a good response to treatment, but responses are sometimes short-lived and further treatment options are needed, justifying further research into inhibitors of this signalling pathway.