Adil Daud, MD: Treatment Options in Melanoma

Which treatment options would you have considered for this patient and what would guide your decision?

Today that decision is a complicated decision because there’s 2 major types of treatments in metastatic melanoma. There’s immunotherapy and there’s targeted therapy. Those are the two major types of treatments that are used. Chemotherapy is not used a lot anymore. So, in terms of trying to decide who is a good candidate for immunotherapy versus targeted therapy, I think the big difference is that targeted therapy, generally speaking, results in a higher response rate while the immunotherapy results in a lower response rate. And there’s different types of patients who benefit from one versus the other. I think normal LDH is a factor that increases your response rate for either immunotherapy or for targeted therapy. I think less than three metastatic sites is known to affect your response rates for targeted therapy and a normal ECOG performance status also is something that’s good in both cases.

I think a lot of times the decision comes down to seeing if somebody has bulky metastatic disease, or needs immediate treatment response, in which case we favor targeted therapy for those patients versus patients who might have the luxury of time, where you might consider immunotherapy first and then use targeted therapy later. I think targeted therapy has higher response rates, but the duration of response is known to be lesser with targeted therapy. With immunotherapy, response rates are lower but the responses are known to be more durable.

So I think to some extent it’s an issue that you need to discuss with the patient and see what is more important to a patient; having a response or having that more durable response and taking that risk of having a lower rate of response. But certainly somebody with normal ECOG performance status or with an ECOG PS of 0 and less than three metastatic sites, normal LDH, I think those are the patients who are known to have long-term benefit from targeted therapy, just to make the picture even more complicated now. I think those are patients where you need to have a careful discussion like with this patient who has M1b disease. We don’t know what her burden of disease is and whether she needs a response immediately or whether she can wait. But this is a reasonable patient to consider for targeted therapy.

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)