• Stéphanie A Blankenstein, Maartje W Rohaan, Willem Martin C Klop, Bernies van der Hiel, Bart A van de Wiel, Max J Lahaye, Sandra Adriaansz, Karolina Sikorska, Harm van Tinteren, Aysegül Sari, Lindsay G Grijpink-Ongering, Winan J van Houdt, WoutersMichel W J MMWJMDepartment of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands., Christian U Blank, Sofie Wilgenhof, Johannes V van Thienen, van AkkooiAlexander C JACJDepartment of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands., and HaanenJohn B A GJBAGDepartment of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands..
• Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
• Ann. Surg. 2021 Aug 1; 274 (2): 383-389.

ObjectiveTo evaluate the potency of short-term neoadjuvant cytoreductive therapy with dabrafenib plus trametinib (BRAF and MEK inhibitor) to allow for radical surgical resection in patients with unresectable locally advanced melanoma.Summary Background DataApproximately 5% of stage III melanoma patients presents with unresectable locally advanced disease, making standard of care with resection followed by adjuvant systemic therapy impossible. Although neoadjuvant targeted therapy has shown promising results in resectable stage III melanoma, its potency to enable surgical resection in patients with primarily unresectable locally advanced stage III melanoma is still unclear.MethodsIn this prospective, single-arm, phase II trial, patients with unresectable BRAF-mutated locally advanced stage IIIC or oligometastatic stage IV melanoma were included. After 8 weeks of treatment with dabrafenib and trametinib, evaluation by positron emission tomography/computed tomography and physical examination were used to assess sufficient downsizing of the tumor to enable resection. The primary objective was the percentage of patients who achieved a radical (R0) resection.ResultsBetween August 2014 and March 2019, 21 patients (20/21 stage IIIC American Joint Committee on Cancer staging manual 7th edition) were included. Planned inclusion of 25 patients was not reached due to slow accrual and changing treatment landscape. Despite this, the predefined endpoint was successfully met. In 18/21 (86%) patients a resection was performed, of which 17 were R0 resections. At a median follow-up of 50 months (interquartile range 37.7-57.1 months), median recurrence-free survival was 9.9 months (95% confidence interval 7.52-not reached) in patients undergoing surgery.ConclusionsThis prospective, single-arm, open-label phase II trial, shows neoadjuvant dabrafenib plus trametinib as a potent cytoreductive treatment, allowing radical resection of metastases in 17/21 (81%) patients with prior unresectable locally advanced melanoma.Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

28 keywords...

hide…