Neoadjuvant Dabrafenib/Trametinib in Stage IIIB/C, BRAF V600–Mutant Melanoma
In the single-center, phase II NeoCombi trial reported in The Lancet Oncology, Long et al found that neoadjuvant dabrafenib plus trametinib produced promising response rates in resectable, stage IIIB/C, BRAF V600–mutant melanoma.
As noted by the investigators, adjuvant dabrafenib plus trametinib improves relapse-free survival in patients with resected stage III melanoma.
Study Details
The study involved 35 patients treated at Melanoma Institute Australia. Patients received dabrafenib 150 mg twice daily plus trametinib 2 mg once daily for 52 weeks, consisting of 12 weeks of neoadjuvant therapy before complete resection of the pretherapy tumor bed and 40 weeks of subsequent adjuvant therapy. The primary outcomes were proportions of patients achieving a complete pathologic response and proportions achieving response according to RECIST at week 12.
Responses
At data cutoff in September 2018, median follow-up was 27 months. After resection and pathologic evaluation, all 35 patients achieved a pathologic response, with 17 (49%) having a complete pathologic response. At resection, 30 (86%) patients had response on RECIST, with 16 (46%) having a complete response, 14 (40%) a partial response, and 5 (14%) stable disease.
Adverse Events
Treatment-related serious adverse events occurred in six patients (17%), consisting of pyrexia in three, syncope in two, and acute kidney injury in one. Treatment-related grade 3 or 4 adverse events occurred in 10 patients (29%), with the most common being pyrexia (12%). Pyrexia of any grade occurred in 80% of patients. One patient had reversible posterior leukoencephalopathy syndrome. No treatment-related deaths were observed.
The investigators concluded, “Neoadjuvant dabrafenib plus trametinib therapy could be considered in the management of RECIST measurable resectable stage III melanoma, as it led to a high proportion of patients achieving a complete response according to RECIST and a high proportion of patients achieving a complete [pathologic] response with no progression during neoadjuvant therapy.”
Georgina V. Long, PhD, of Melanoma Institute Australia, University of Sydney, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by GlaxoSmithKline; Novartis; National Health and Medical Research Council, Australia; and Melanoma Institute Australia. For full disclosures of the study authors, visit thelancet.com.
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