Another block of presentations regarded neoadjuvant therapy of locally advanced melanomas. Some preliminary results of trials with BRAF and MEK inhibitors were presented.
Prof. Haanen presented the first results of the Reductor trial on 13 patients with initially unresectable or locally advanced (with high chance of a positive margin) BRAF-positive stage IIIC melanoma . Patients were treated with dabrafenib and trametinib for 8 weeks; 11 patients underwent surgery and, finally, 9 achieved R0 resection (9/13 = 69% R0 resectability rate). Of these 9 patients (with median follow-up of 9 months; range 3–22 months), 6 had a recurrence and 3 remain disease free.
Dr Amaria discussed a trial of neoadjuvant (8 weeks) plus adjuvant (44 weeks) therapy with dabrafenib and trametinib versus standard upfront surgery . In 21 patients, neoadjuvant and adjuvant dabrafenib/trametinib (14 patients) significantly improved relapse-free survival over the standard arm (7 patients; P < 0.0001). Among 12 patients assessed after preoperative therapy, complete pathological response was observed in 7 (58%).
Prof. Long presented the results of a trial with neoadjuvant and adjuvant dabrafenib plus trametinib combination in BRAF-mutated stage III bulky disease resectable melanoma patients who were treated preoperatively for 12 weeks and postoperatively up to 52 weeks . In 30 assessed patients after 12 weeks of therapy, pathological and PET-FDG metabolic complete response was achieved in 50%. Nine patients (30%) recurred during follow-up, with a median time to recurrence of 51 weeks.
These results of neoadjuvant targeted therapy for locally advanced BRAF-mutated stage IIIC melanomas seems promising. On the other hand, the OpACIN trial with neoadjuvant combined immunotherapy (ipilimumab + nivolumab) achieved an overall response rate of 80% in 10 patients, albeit accompanied by high toxicity.