Jeffrey Weber, MD, PhD: The Association Between Durable Response and Low Disease Burden

Could the durable response for this patient be associated with her low disease burden?

This patient’s case brings up the conundrum that we face when we have either a CR or a near CR to targeted therapy. What do you when someone has been on treatment for literally, in this case, years, three years and probably went into remission very early because this was a patient with a favorable outcome. Even though they had M1c disease, the LDH was normal, the PS was zero, and I would venture a bet if you added up the disease burden, it was pretty moderate, very or even minimal. So what do you do at year 3? Again, we don’t have enough experience with compiling patients who have been on all BRAF/MEK randomized trials, which thousands of patients by the way, several thousand, and ask what happened when someone stopped either out of choice or because of toxicity, how well did they do?

I would venture a guess and we’re off in a data-free zone, by the way, I would venture a guess that those patients did well. So I would tell the patient it would be safe to stop treatment at year 3 in complete remission. I think somebody who is a CR is probably going to stay there for a long time, and it probably doesn’t matter how they get there, whether it be chemo, or targeted therapy, or immunologic therapy. Again, it would be nice to mine the databases of the sponsors who have done these big randomized trials to ask what happened to those patients. But, in the absence of those data, I would feel comfortable telling this patient they could stop with the thought that they could either be re-induced after some period of time if, God forbid, they relapsed with BRAF/MEK, or they could go on to immunotherapy.

I think a patient with a low disease burden, good performance status, and normal LDH is going to be one of those patients who has a good chance of going into a CR and staying there. So I think there’s clearly an association between those factors as evidenced by the recent publication in theJournal of Clinical Oncology

CASE: Metastatic Melanoma

Sarah is a 50-year-old Caucasian postal worker who presented to her primary care physician with multiple, skin-colored nodules and palpable lymph nodes. .

• A workup, biopsy, and mutation test was conducted, which revealed BRAF V600E mutation-positive melanoma that had metastasized to the lymph nodes, subcutaneous tissue, and right adrenal gland.    
• ECOG performance status is 0 and her LDH levels are normal.

The patient was started on the combination of dabrafenib and trametinib. She experienced a durable complete response and has remained on therapy for 36 months.