Melanoma Progression Following Adjuvant Therapy


Sanjiv S. Agarwala, MD: Before we end adjuvant therapy, though, I have 1 quick question. People are getting adjuvant therapy now. Some of them will relapse, and they would require treatment. What do you consider to be refractory? The magic number is within 6 months for this, right? Six months beyond stopping adjuvant therapy relapse. Is that a treatment-naïve patient or not, Dr Eggermont? Is 6 months you’re feeling as well? Relapsing on treatment again?

Alexander Eggermont, MD, PhD: No, relapsing on treatment, there is obvious resistance. The 6 months is a best-guess type of period to work with in which you can restart with anti—PD-1 [programmed cell death protein 1] first. At least in BRAF wild-type patients, that’s what you would be doing, or you would give them the combo to enhance the chances.

Sanjiv S. Agarwala, MD: If a patient is BRAF-positive, and you give them BRAF-targeted therapy in the adjuvant setting and they relapsed 1 year later, would you give them immunotherapy or BRAF-targeted therapy again?

Caroline Robert, MD, PhD: No, I would try immunotherapy.

Sanjiv S. Agarwala, MD: What about the other way around? Someone who has relapsed 1 year ago from immunotherapy.

Caroline Robert, MD, PhD: We discussed this by imagining a very slowly growing melanoma. Maybe it will take more than 6 months, but there was no effect maybe of the anti—PD-1. It becomes visible just at 7, 8 months.

Sanjiv S. Agarwala, MD: So you’d rather switch to the other type of treatment if possible, right?

Caroline Robert, MD, PhD: We suppose that after 6, 12 months it has been maybe a benefit, and the benefit is lost, so we can try again. But all that means is, we need to have a better biomarker than our intuition.

Dirk Schadendorf, MD, PhD: But I think the concept now in melanoma is to have a long-term tumor control or possibly even cure. I mean, if you have a relapse, obviously your first approach was not successful. I think it’s reasonable to consider switching the mode of action, and I think that’s the first thing to do. Then you can go back to the other modality if this is not going to work.

Alexander Eggermont, MD, PhD: Exactly.

Sanjiv S. Agarwala, MD: When you have a choice, you should take it.

Alexander Eggermont, MD, PhD: It’s what we would we do.

Caroline Robert, MD, PhD: Yeah.

Dirk Schadendorf, MD, PhD: And maybe next year or in 2 years, we will have triple combinations which then would…

Alexander Eggermont, MD, PhD: Which thus far are not superior to the combination of anti—PD-1 plus low-dose CTLA4.

Sanjiv S. Agarwala, MD: On that note, let’s go to metastatic melanoma and talk about exactly that.

Alexander Eggermont, MD, PhD: No, you need to say 1 word about stage II melanoma. Because from the adjuvant trials in sentinel-node-negative patients, we know there’s a small group of patients who will relapse. And that group of patients is a curve that ends up at 5 years, 25% to 30% will have relapsed. The rest is cured.

Sanjiv S. Agarwala, MD: With surgery alone.

Alexander Eggermont, MD, PhD: Yeah. The point is that for the sentinel-node-negative patient population, you can do a trial only if you up front declare by using a profiler. And there are a couple of profilers now that you can use in characterizing the primary melanoma that identifies actually this 25% to 30%. You must declare up front that this is your patient group of interest. And I bet you that the hazard ratio will be exactly the same as in stage III melanoma. And the other patients can be spared adjuvant therapy with anti—PD-1s or whatever it is. All adjuvant trials in stage II sentinel-negative-node patients must have another classifier to identify the group at risk. Otherwise we will end up treating the whole population and all nations from the day after birth with some drugs.

Sanjiv S. Agarwala, MD: Well, we need a better biomarker for…

Alexander Eggermont, MD, PhD: It’s our responsibility to make sure that will not happen. And so trials need to be adapted for this new knowledge. And this is the discussion that we will have with the FDA because we must, at the same time, protect our patients. That is our duty.

Sanjiv S. Agarwala, MD: I agree.

Transcript Edited for Clarity

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