Metastatic Melanoma: Considering Factors for Treatment

Michael A. Davies, MD, PhD:So, this is a patient who presents with newly diagnosed stage 4 melanoma with evidence of involvement of the lungs, but no other organs. There’s the presence of aBRAF V600Emutation and a normal serum LDH level. There are many different available treatment options for this patient, including multiple targeted therapies and multiple immune therapies. At this point in time, for patients who present with aBRAFmutation, we actually don’t know if the right approach is to treat initially with targeted therapy or immune therapy. As to date, there have been no head-to-head randomized trials comparing these different therapeutic approaches in patients withBRAF-mutant disease.

ForBRAF-mutant metastatic melanoma patients, a number of considerations must go into the decision about the appropriate initial therapy. It should be noted that both targeted therapies and immune therapies have been shown to work after the failure of the other therapeutic modality. So, we tend to emphasize the multiple different therapeutic options that are available for this patient, both at this time and in the future.

In terms of picking the initial therapy, we often will evaluate the aggressiveness of the disease that the patient has. What is the size of the tumor burden? What is the extent of site involvement? What are the serum LDH values? There’s higher tumor burden, higher extent of disease, and higher LDH, being consistent with a more aggressive disease and therefore probably necessitating more aggressive treatments. For patients who actually have low burden of disease and normal LDH, we know that those patients have very good outcomes, whether we use targeted therapies or immune therapies.

We also will consider the comorbidities of the patients. There are certain factors that will push us toward or away from certain therapies, such as the presence of coexisting autoimmune conditions, which may cause us to move more toward using targeted therapies as compared to immune therapies.

And finally, specifically, as we think about different immune therapy options for this patient, we may consider things like her comorbidities and her social support structure. Certain immune therapies, like TD1, have a very low risk of toxicities, but other therapies like the ipilimumab/nivolumab combination have a very high risk of toxicities and, therefore, are safer to give in patients who have a good support system in place.

Transcript edited for clarity.

April 2017

• A 52-year-old female presented to her dermatologist with a pigmented lesion which had recently become darker; she had it removed for cosmetic reasons
  • Pathology revealed a melanoma with a depth of 2.3 mm
  • Genetic testing;BRAF V600mutation-positive
• LDH, WNL (174 UI/L)
• She underwent wide local excision and sentinel node mapping; staining is positive for melanoma in the right axillary node
• Complete dissection of the right axilla reveals no additional involved nodes
• CT of the chest, abdomen, and pelvis showed multiple masses in both lungs, the largest being 5 mm
• She underwent core-needle biopsy of the largest lung lesion
  • Pathology revealed metastatic melanoma
  • Mutation testing:BRAF-positive
• The patient is started on dabrafenib 150 mg bid and trametinib 2 mg qd