Immunotherapy in BRAF Wild-Type Advanced Melanoma

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Various treatment strategies have emerged for patients with BRAF wild-type advanced melanoma. In this setting, treatment can be individualized through the use of a patient’s performance status and whether they have CNS disease, suggests Howard Kaufman, MD. For patients who are ineligible for a clinical trial, Kaufman typically starts with high-dose interleukin-2 or ipilimumab. PD-1 inhibitors are reserved for second-line therapy in these patients, he suggests.

Patients who have BRAF-negative tumors and experience disease progression on multiple agents are challenging to treat, notes Robert Andtbacka, MD. Once immunotherapy approaches have been utilized, good responses can still be achieved using chemotherapy. Additionally, radiotherapy may induce an abscopal effect in some patients, suggests Omid Hamid, MD.

Importantly, there doesn’t appear to be cross-resistance among immunotherapies, adds Kaufman. A patient that doesn’t respond to one immunotherapy may respond to the next one. Although much progress has been made with checkpoint inhibitors, many questions remain, such as who will respond to PD-1 inhibitors, and in what sequence should they be given with other agents. It appears that baseline tumor size may be the most important predictive factor, explains Richard Joseph, MD.

Questions remain concerning how exactly to use PD-L1 expression as a predictive marker for nivolumab and pembrolizumab, previous exposure to ipilimumab, and whether tumor location or the site and extent of metastases matter. The answers to these questions will fall under the sphere of personalized medicine, which is where the treatment of melanoma needs to be headed.

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Daniel Olson, MD
Vishal Patel, MD, FAAD, FACMS, associate professor, Dermatology, George Washington (GW) School of Medicine & Health Sciences
Omid Hamid, MD, professor, medicine, Cedars-Sinai; director, Clinical Research and Immunotherapy, director, Cutaneous Oncology and Melanoma, The Angeles Clinic and Research Institute