Doctors Weigh Patient Goals Instead of ‘Dictating’ Melanoma Treatment

A discussion between patient and doctor is important when considering treatment goals, an expert told CURE®.

Treatment via dual checkpoint inhibitors was associated with an increased likelihood of pathological and radiologic responses for patients with high-risk resectable (removable by surgery) melanoma, researchers found.

However, treatment with presurgical standalone anti-PD1 therapy was associated with a lower risk of severe immune-related side effects, while alternative dosing of with dual checkpoint inhibitors was associated with lower immune-related side effect risk with no major difference in efficacy.

“It [then] becomes a discussion with the patient, [of] 'What are you looking for? Are you looking for a complete response?'” said Dr. Ankit Mangla, assistant professor, Department of Medicine, School of Medicine at Case Western Reserve University School of Medicine and a member of the Developmental Therapeutics Program at the Case Comprehensive Cancer Center in Cleveland. Mangla was among the researchers who analyzed the results of a half-dozen clinical trials and published their findings in JAMA Oncology.

“Patients, sometimes they walk in and say, 'It doesn't matter what happens to me, but I want this tumor gone,'” Mangla said. “So with that kind of a patient, you can … say ‘Although your risk of having a side effect is high, the chances of achieving this tumor going into complete remission is also high with the two drugs. If I have to use the two drugs, then this is the regimen I'm going to use, which is [the alternate dosing]. I think that is one definite point that is coming from this data set.

“Then, some patients walk in, and they say, 'OK, we will take the medicine, but we want no side effects.’ For that patient, I think this data set is again useful in telling them that a single agent may not take you all the way but will definitely be less aggressive in giving you side effects."

There were 573 patients with stages 3 and 4 melanoma in the study who were treated with either single-agent Keytruda (pembrolizumab) or with dual checkpoint inhibitors. The National Cancer Institute defines checkpoint inhibitors as a treatment that prevents cancer cells from suppressing the patient’s immune system, thereby allowing the body to fight and kill cancer cells.

“If you look at the overall results, using two agents is definitely more effective in achieving a pathologic complete response [no evidence of cancer] compared to a single agent,” Mangla said. “Now, why are we obsessed with pathologic complete response? We are obsessed with it because that's the patient that's going to live long [and] is going to be alive at the end of five years. But then, at the end of the day, we don't want to damage an organ as well. We want the patient to receive that surgery because in stage three melanoma surgery is still the primary treatment, we don't circumvent surgery by using these drugs upfront, we still want to take the patient to surgery — and that's where we found single-agent anti-PD1 monotherapy was actually better in terms of giving side effects to the patient.”

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Ultimately, the question of prioritizing efficacy or side effect burden is only one that patients can answer for themselves, as Mangla explained.

“Most of us who are of a younger generation, we are doing away with the patriarchal approach. We are not dictating,” he said. “Most of the times when I tell patients that, ‘It's your choice,’ they kind of are taken aback because they really don't have an understanding of the whole field. And they look up to our expertise to explain this. But in my practice, and in the way I was trained and the people who trained me and their practices also, I saw this quality where we guide the patient, but we don't make the choices for them. We don't really say that this is what you're supposed to do. So that's where I think this discussion is very important and this paper will help them decide for themselves as to what is the priority in their lives.

“Like, I always tell this to patients, immunotherapy side effects are not consistent. If I give chemotherapy to 10 people I know all 10 people will have side effects to various degrees, maybe some will have more some will have less, [but] immunotherapy is not like that. If I give 10 people immunotherapy, single agent Keytruda ballparks gives major side effects to only 20% to 30% of people. Most people will feel tired, because their immune system is working hard to get rid of the cancer. But they may not experience any major side effects and quality of life is actually very good on checkpoint inhibitors compared to somebody who's on chemotherapy. So it's a discussion with the patient as to what exactly do you want?”

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