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Moderator Omid Hamid, MD, begins by reviewing the best approach to adjuvant treatment for resectable malignant melanoma. For BRAF-positive disease, Anna Pavlick, DO, preferentially offers patients a clinical trial with BRAF-targeted therapy or immunotherapy. Howard Kaufman, MD, adds that radiotherapy is also an option, if there is minimal residual disease in a favorable location after resection.
Adjuvant approaches have not been very successful in melanoma, with a high rate of disease recurrence, Robert Andtbacka, MD, notes. For this reason, neoadjuvant approaches are being explored. Immune-modulating agents have been evaluated for unresectable tumors and are now being looked at in the neoadjuvant setting. One such promising therapy is talimogene laherparepvec, an injectable oncolytic immunotherapy being studied in patients with resectable stage IIIb, IIIc, and stage IV M1a melanoma.
Getting the patient to resection is always the goal, Kaufman adds. Tumor debulking can be achieved with a BRAF inhibitor or an anti-BRAF/MET combination for a BRAF-mutated tumor. Systemic immunotherapy is also potentially useful in this situation. There has been some success with this approach with the CTLA-4 inhibitor ipilimumab, agrees Richard Joseph, MD.
Whether or not to continue BRAF inhibition after resection is highly controversial, says Pavlick. This decision could be guided by the presence and genetic make-up of residual disease, since many patients respond to neoadjuvant therapy in one lesion but not another, suggests Andtbacka. Surgery is important in these cases to render the patient disease-free. Radiation therapy also has a role. Kaufman adds that at his center, discontinuation of BRAF inhibition in patients with no evidence of disease after surgery has been evolving. BRAF inhibition can be restarted at recurrence if needed, Kaufman notes.