ONCAlert | 2018 ASCO Annual Meeting
Melanoma Case Studies

Jeffrey Weber, MD, PhD: Predicting Which Patients Will Experience Durable Responses to Targeted Therapy

Jeffrey Weber, MD, PhD
Published Online:Aug 18, 2016
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.

Metastatic Melanoma with Jason Luke, MD and Jeffrey Weber, MD, PhD: Case 2

Metastatic Melanoma with Jason Luke, MD and Jeffrey Weber, MD, PhD: Case 1
Metastatic Melanoma with Jason Luke, MD and Jeffrey Weber, MD, PhD: Case 2

What can be done to help predict which patients might experience durable responses to targeted therapy, like Sarah's?

Just the simple assessment of LDH, probably more than anything else, plus the disease burden (and those two things are connected, by the way), those two very clinical, old-world assessments will tell you who’s going to do well with targeted therapy and who’s not. I can assure you, someone with an LDH more than twice normal, is going to have a very short remission. They may have a good response, but that remission is going to be short, and the PFS is going to be very low. Someone with an LDH that’s absolutely normal, with a couple of small pulmonary metastases that are each about a centimeter, that patient is going to do really well because they’ll also have a PS of zero, and they’ll be in good shape.

I think that, at the end of the day, we’re going to need more molecular indicators that will be derived by an approach where we’ll be biopsying everybody who relapses. And not only that—we’ll be collecting what we call liquid biopsies from patients in the midst of treatments and biopsies from those in midstream to try to find out what pathways in the tumor, and in the circulation and in the host, are altered. And do they give early warning of relapse, so you can add another drug or subtract one drug and add another? It helps give you more information about the etiology or the cause of the development of drug resistance. There’s been a lot of work done in the drug resistance world lately, and the best information has come from looking at the tumor. But I think you’re also going to find information from querying the host.

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.

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