Oral 1.02: Sunitinib in patients with advanced thymic epithelial tumors (TET)

Background: No standard treatments are available for advanced thymic epithelial tumors (TET) after failure of first-line platinum-based chemotherapy. Sunitinib is a potent oral tyrosine kinase inhibitor of VEGFR, KIT and PDGFR. In a single arm phase 2 study of sunitinib after at least one previous line of chemotherapy, a 26% of partial response rate (PR) was reported in thymic carcinoma (TC) and 6% in thymoma (T), with a median progression free survival (mPFS) of 7.2 months and 8.5 months, respectively. We investigated if off-labelled prescription of sunitinib in this population induced the same efficacy signal.

Methods: We investigated the RYTHMIC database of the French thymic malignancies network. We reviewed advanced T and TC patients who were treated with sunitinib in order to evaluate patient’s outcome.

Results: From October 2011 to January 2015, 28 patients from 7 institutions were identified (20 TC and 8 T). Nine out of 28 patients (32%) were females and median age was 49.7 years. Fifteen patients (54%) received sunitinib in ≥4^th line of treatment. Two patients received sunitinib in 1^st line treatment (1 T and 1 TC). The 37.5 mg was the initial dose of sunitinib in 16 patients. In the whole population, the disease control rate (DCR) (partial/complete response and stable disease) was 61%. DCR was 55% in TC (11 out of 20 patients) and 75% in T (6 out of 8 patients). The ORR rate was 21% [4 out of 20 patients with TC (20%) had a PR; and 2 out of 8 patients with T (25%) had PR]. Of note, PR to sunitinib was independent of treatment line (1 patient at 1^st lines, 1 patient at 3^rd line, 2 patients at 4^th line and 2 patients at ≥5^th line) and sunitinib initial dose (for 3 patients initial dose of sunitinib was 37.5 mg and for 3 patients was 50 mg). Three TC patients were c-KIT positive, without a clear relationship with response rate (1 PR, 2 PD). The mPFS in whole population was 103 days. For TC the mPFS was 87 days and 139 days for T. The median overall survival (OS) in the whole population was 175 days, with prolonged OS in T vs. TC (403 vs. 166 days). Sunitinib adverse events were manageable and tolerable. Eight patients stopped sunitinib due to toxicity of whom two had achieved PR.

Conclusions: Sunitinib is an active treatment in TET irrespective of histological subtype and treatment line, even in a heavy pre-treated population, supporting antiangiogenic therapies as an alternative treatment option for these patients.

Keywords: Efficacy; thymic; tumors; sunitinib