A phase II randomized study of adjuvant imatinib versus high-dose interferon alpha-2b for resected high-risk c-kit mutated melanoma.

Abstract

e20027 Background: Imatinib, a selective inhibitor targeting Abl as well as C-Kit and the platelet-derived growth factor receptor, has been tested for the efficacy and toxicities in metastatic melanoma patients harboring mutations in C-Kit gene. High-dose interferon for one year (HDI) is the FDA approved adjuvant therapy for patients (pts) with high-risk melanoma. This study (NCT01782508) aims to see whether imatinib is more effective than interferon alfa-2b in adjuvant therapy for patients with C-Kit mutated melanomas. Methods: This study enrolled C-Kit mutated(exon 9,11 or 13)pts who were high risk (stage IIB to stage IIIC) and randomized them to receive either imatinib (400mg daily for a year) or HDI (interferon a-2b 15X106 U/m2 d1–5/wX4w + 9X106U tiwX48w) in the absence of disease progression or unacceptable toxicity. 40 pts of each group were planned to enroll. Routine tests including blood tests, medical history updates, physical exams and Brain/Chest/Abdomen/Pelvic CT were performed every 2 months. The endpoints were recurrence-free survival (RFS) and overall survival. Results: Through Jan 2013,7 pts were recruited F3 in imatinib arm and 4 in HDI arm. The three pts received imatinib haven’t had recurrence or metastasis. The RFS were 6m+ (Exon 11: W577S), 5m+ (Exon 11: L576P), 5m+ (Exon 11: L576P) respectively. Two pts have already had lung or regional lymphnode at 4 months (Exon 13: K642E) and 5 months (Exon 11: V560D) in the HDI arm. The other two pts (both Exon 11: 579 insert) in the HDI arm were still disease free for 6 months. The toxicities were consistent with the usual reported studies. Conclusions: In the C-Kit mutated melanoma pts, it’s promising that imatinib may provide more beneficial effect than HDI for high-risk melanomas. (Supported by the National Natural Science Foundation of China (30973483, 81172196, 81102068.) Clinical trial information: NCT01782508.