A phase II study on the efficacy of regorafenib in treating patients with c-KIT-mutated metastatic malignant melanoma that progressed after previous treatment (KCSG-UN-14-13)
Mené sur 23 patients atteints d'un mélanome présentant des mutations au niveau du gène c-KIT et de stade métastatique, cet essai de phase II évalue l'efficacité, du point de vue du taux de contrôle de la maladie, et la toxicité du régorafénib après au moins une première ligne thérapeutique
Background: c-KIT mutations are found in approximately 15% of patients with malignant melanoma in the Asian population. Regorafenib, an oral multikinase inhibitor, acts against both wild-type and mutant KIT. Objective: This multi-institutional, phase II, single-arm study aimed to evaluate the efficacy of regorafenib against metastatic malignant melanoma harboring c-KIT mutations. Methods: Patients with metastatic melanoma positive for c-KIT mutations, upon progression after at least one line of systemic treatment, were enrolled. Patients received oral regorafenib 160 mg once daily for 3 weeks (4-week cycle). The primary endpoint was disease control rate (DCR), and secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: In total, 23 patients were enrolled. c-KIT mutations were frequently reported in exon 11 (14/23, 60.9%), followed by exons 13, 17, and 9 in 5 (21.7%), 5 (21.7%), and 2 (8.7%) patients, respectively. DCR at 8 weeks was 73.9%, with 2 patients (8.7%) achieving complete response, 5 (21.7%) achieving partial response, and 10 (43.5%) showing stable disease. ORR was 30.4% (7/23). The median follow-up period was 15.2 months (95% confidence interval [CI], 10.0–21.5), and median OS and PFS were 21.5 months (95% CI, 15.1–27.9) and 7.1 months (95% CI, 5.0–9.2), respectively. Circulating tumor DNA analysis in selected patients showed high c-KIT correlation (85.7%) with tissue-based tumor mutational profiles. The most common adverse events (AEs) were skin reactions, including palmar-plantar erythrodysesthesia (52.2%), and grade 3 AEs were reported in 39.1% (9/23) of the patients. Conclusion: Regorafenib in second- or later-line settings demonstrated significant activity in patients with metastatic melanoma harboring c-KIT mutations.