Advances in the Treatment of Malignant Melanoma - Episode 9

Systemic Therapy for Metastatic Melanoma

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Jeffrey S. Weber, MD, PhD: Let’s move on from adjuvant to neoadjuvant. Let’s talk about systemic approaches. Back to you, Adil. It’s the same question that we think about in the adjuvant mode. How do you make decisions in choosing therapy, BRAF versus immunotherapy, based on if it’s a BRAF-mutated or a BRAF wild-type patient? What are the biomarkers that help you to make the choice?

Adil Daud, MD: That’s a great question, and I loved the previous discussion that Jason Luke and Sunandana Chandra were having about adverse events. In terms of neoadjuvant, I lean toward immunotherapy. That has to do with some biases from trials in terms of thinking that immunotherapy will have more lasting benefit. I have to say, parenthetically, that we understand a lot more about immunotherapy response, and we understand the mechanism of immunotherapy response a lot better than we understand BRAF-mutated patients who will have a lasting response versus who won’t have a lasting response. There’s been some interesting biomarker work done in BRAF-mutated patients too. Today I would say that none of us can really predict, given the BRAF-mutated patient, who’s going to have a lasting benefit versus who’s going to have some kind of bypass pathway.

I feel like in the neoadjuvant space, unless somebody has a history of previous adverse events—colitis, multiple sclerosis, or some major issue—I lean toward using immunotherapy. Then the choice between using single-agent or double-agent immunotherapy comes down to what I think is likely to work, how bulky the tumor is, and how urgent the treatment seems to be. Most of our neoadjuvant patients today are not organ sparing. As Jason was mentioning earlier, you’re not really converting non-surgically resectable to resectable. You’re just basically trying to see what works better. Some of the ASCO [American Society of Clinical Oncology] trials are interesting in the sense that they are suggesting 2 cycles or a shorter duration of treatment is enough. Alex Huang’s trial also suggested that 1 single dose might be enough.

I treated this 1 patient—and I mention this because it just happened. I gave her 6 months of treatment with single-agent nivolumab. She had a complete response, pathologic complete response [CR]. Then we had a long discussion. I was like, “Yeah.” She was like, “It’s really important for me to have maximum survival.” I was like, “OK, we’ve given 6 months. Why don’t we give you 6 months more adjuvantly afterward?” In the 6 months, her sugar started rising, and then she developed type 1 diabetes. Now I’m just cringing inside, and I’m thinking maybe I should have stopped with the path CR and not done that extra few months of treatment. Maybe she wouldn’t have type 1 diabetes. I feel like 1 lesson for me from this year’s ASCO Annual Meeting is that maybe shorter duration is OK. I hope I don’t overlearn that lesson and have the opposite problem. Maybe the 1 advantage of neoadjuvant therapy is that we can get by with shorter, less intense treatment.

Jeffrey S. Weber, MD, PhD: Do you feel the same way about metastatic therapy? Meaning, do you tend to lean to immunotherapy first, rather than targeted therapy?

Adil Daud, MD: I do. I just want to check my biases here. I feel like the data are maybe not fully supporting my position. I feel like immunotherapy offers longer-term success.

Transcript Edited for Clarity