Adil Daud, MD: Optimal Sequencing for BRAF-Mutant Melanoma

What are optimal sequences currently for a patient like Michelle, with BRAF-mutant M1b stage melanoma?

What we know is that if you consider patients who had targeted therapy first followed by immunotherapy, that may reduce response rates to immunotherapy. Vice versa, if you consider immunotherapy first followed by targeted therapy, we think in that situation you probably don’t reduce response rates. So many people think that in a person with excellent performance status, low burden disease, somebody who has the luxury of time, you might consider using immunotherapy first to give them that possibility of a long duration response or cure. I mean cure is a difficult word to use in oncology, but at least a long duration response is a possibility. For somebody with a high burden of disease, maybe a tumor that is affecting the spine, a spinal cord or causing some immediate issue, immunotherapy may not be best. Like with her M1b disease, if that was causing shortness of breath, that would be a reason to favor targeted therapy maybe versus if it was just some small lung nodules that weren’t causing any symptoms, you might consider immunotherapy for that type of person.

CASE: Metastatic Melanoma

Michelle is a 55-year old who was referred by her primary care physician to receive a biopsy for a suspicious mole during a routine visit. Results of the biopsy and other subsequent tests revealed that she had an M1b stage tumor (lung metastasis and a less than ULN LDH level). Her ECOG PS is 0.

• Initial BRAF testing using a laboratory-developed test was negative for BRAF V600E L

She was referred from the community setting to a tertiary center, at which point a second test was conducted using the bioMérieux HxID-BRAF kit. This assay was positive for the BRAF V600K mutation

• Following the finding ofBRAF-positivity, Michelle was prescribed the combination of dabrafenib (150 mg BID) and trametinib (1 mg daily)