Phase II study of everolimus in patients with thymoma and thymic carcinoma previously treated with cisplatin-based chemotherapy.

Abstract

7527 Background: Alterations of the serine-threonine kinase mammalian target of rapamycin (mTOR) signalling pathway are common in cancer, and thus mTOR is being actively pursued as a therapeutic target. In particular, mTOR is emerging as a potential target, following tumor responses observed in phase I trials, with recent data from several groups. The aim of this study is to determine the activity of Everolimus monotherapy in patients (pts) with advanced or recurrent thymoma (T) or thymic carcinoma (TC) previously treated with cisplatin-containing chemotherapy. Methods: Pre-treated T and TC pts were prospectively enrolled in single arm, single-stage, open label, multicentre, phase II trial. Pts received continuous treatment with oral everolimus 10 mg once daily until documented disease progression, unacceptable toxicity, or patient refusal. Tumour assessment was done every six weeks, safety was assessed every 21 days. A Fleming phase II trial was designed considering a disease control rate (DCR) of 40% or lower as clinically unworthy, whereas a rate of 60% or higher was considered of potential interest, α=β=0.10. It was calculated that 21 pts with disease control would be observed in the first 41 evaluable pts. Progression free survival (PFS), overall survival (OS), and safety were also evaluated. Results: Results of the first 35 enrolled pts are presented. Patient characteristics are as follow: median age is 51 years (range 37;81), male/female 20/15 (57%/43%), TC/T 12/23 (34%/66%), and locally advanced/metastatic disease 9/26 (26%/74%). We observed complete remission (CR) in 1 patient (TC), partial response (PR) in 3 pts (2TC/1T), and stable disease (SD) in 21 pts (16T/5TC), for a total of 25 pts who reached DC.With a median follow up of 10 months, median PFS was 12.1 months, while median OS was 24.0months. Seven pts (20%) presented a serious adverse event but only 3 of them permanently discontinued treatment. Conclusions: The primary end-point of this study was reached. These results suggest that Everolimus is able to achieve a satisfactory number of DC in this setting of pts. The efficacy should be better evaluated in subsequent larger study phases. Clinical trial information: NCT02049047.