Neoadjuvant Dabrafenib Plus Trametinib for Stage III Melanoma
Posted: Monday, July 8, 2019
The combination of neoadjuvant dabrafenib and trametinib seems to be an effective treatment for patients with stage III melanoma, and the therapy improves relapse-free survival in these patients. However, compared with patients treated with neoadjuvant anti–PD-1 immunotherapy, those treated with this combination therapy still had a high risk of relapse, according to Georgina V. Long, PhD, of the University of Sydney, Australia, and colleagues. These single-center phase II trial (NeoCombi) findings were published in The Lancet Oncology.
“Neoadjuvant dabrafenib plus trametinib therapy could be considered in the management of [Response Evaluation Criteria in Solid Tumors (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 pathological response, with no progression during neoadjuvant therapy,” concluded the authors.
From August 2014 to April 2017, 35 patients with stages IIIB to C, BRAF V600mutant melanoma were enrolled in the trial. Patients received 150 mg of dabrafenib twice daily plus 2 mg of trametinib once daily before resection. At the end of data collection, the median follow-up was 27 months.
After pathologic evaluation and resection, all 35 patients had achieved a pathologic response, and 49% of patients had a complete pathologic response. At the time of resection, 86% of patients achieved a RECIST response, with 46% and 40% of patients achieving complete and partial RECIST responses, respectively. Five patients had stable disease at the time of data collection, and no patients experienced disease progression.
In total, 6 of the 35 patients had treatment-related serious adverse effects, including pyrexia, syncope, and acute kidney injury. Grade 3 or 4 adverse effects occurred in 29% of patients, most commonly pyrexia (12%). There were no treatment-related deaths reported.
Disclosure: The study authors’ disclosure information may be found at thelancet.com.