OA11.05 Phase II Study of Sunitinib in Patients with Thymic Carcinoma Previously Treated with Platinum-Based Chemotherapy (KOSMIC Trial)

Only one prospective study in western population suggests sunitinib is an effective treatment for thymic carcinoma (TC). We evaluated the clinical efficacy and toxicity of sunitinib in Korean patients with metastatic TC after platinum-based chemotherapy. Between Sep 2015 and May 2017, we enrolled 25 patients with histologically confirmed platinum-refractory TC at three academic hospitals in Korea. Patients were eligible if they had progressive disease after one or more cytotoxic chemotherapy including platinum-based regimen, at least one measurable disease by RECIST (v1.1) and adequate organ function. Patients received 50mg of sunitinib on an alternative schedule (2weeks of treatment followed by 1 week without treatment) until objective progression of disease or unacceptable toxicity of treatment. The primary endpoint was objective response rate and tissue and blood specimen were collected for NGS panel analysis (170 genes, Hybrid capture based method). This trial was registered with Clinicaltrials.gov, number NCT 02623127. A total of 25 patients were enrolled in this trial. Median age was 62 (39-75) and 19 (76%) patients were male. Most patients (20 patients, 80%) received sunitinib as 2nd line treatment. Two patients discontinued treatment earlier than first tumor assessment due to toxicity and excluded from efficacy analysis. Among 23 evaluable patients, 5 (21.7%) patients had partial response and 16 (69.6%) patients achieved stable disease. Disease control rate (PR+SD>6m) was 56.5%. Median progression-free survival (PFS) was 15.2 months and 6 patients had ongoing responses at the time of analysis. Most common treatment-related adverse events were mucositis (12 patients, 48%), fatigue (9 patients, 36%), and hand-foot syndrome (9 patients, 36%). The most common grade 3/4 toxicity was thrombocytopenia (4 patients, 16%). Seventeen (68%) patients needed at least one dose reduction due to adverse events. Genomic profiling with NGS cancer panel revealed 2 patients with pathogenic KIT mutation (c.1879+1G>A and c.1671 G>C) who had PFS of 21.3m and 9.3m, respectively. In 15 patients with tumor tissue gene panel results, high tumor mutation burden (TMB) was significantly associated with longer PFS (median PFS not reached in TMB ≥30/MB vs. 3.45m in TMB <30/MB, P=0.03). Sunitinib with 2/1 schedule is an active treatment for TC after platinum-based chemotherapy.