Refining Treatment Approaches and Advancements in High-Risk Melanoma

Although the 2025 ASCO Annual Meeting did not generate practice-changing within the realm of melanoma care, the meeting highlighted practice-affirming data, according to Dr. Vincent Ma, a faculty member in the Division of Hematology, Medical Oncology and Palliative Care at the University of Wisconsin.

“[Based on] the findings of the [RELATIVITY-098] study, the standard of care still remains that for patients after resection of stage 2, stage 3, or stage 4 melanoma, anti-PD-1 monotherapy should still be the standard of care, rather than a two-drug immunotherapy regimen,” Ma said when discussing this research in an interview with CURE, reaffirming the current standard-of-care for patients with this disease.

In the interview, he discussed some of the most treatment updates for patients with high-risk and advanced melanoma.

Ma is also an assistant professor within the Department of Medicine and is a faculty affiliate of the Department of Dermatology, all at the University of Wisconsin, School of Medicine and Public Health.

CURE: What were some of the most notable treatment updates for patients with melanoma that were shared at the 2025 ASCO Annual Meeting?

Ma: At ASCO this year, there were several interesting updates regarding the management of advanced-stage melanoma, as well as studies investigating whether there is a role for treatment after complete surgical resection of melanoma. Overall, [the meeting] was more affirming of clinical practice rather than presenting practice-changing data for melanoma.

What do we currently know about the optimal duration of immunotherapy for advanced-stage melanoma, and were any updates shared at the meeting?

One of the interesting studies presented this year was the DANTE trial. This was a phase 3 study examining whether two years of immunotherapy — the current standard minimum — is more effective than one year for patients with advanced-stage melanoma.

To provide some background, the current standard for treating advanced-stage melanoma involves a minimum of two years of immunotherapy because that's how these drugs were studied in large-scale clinical trials. However, both providers and patients often wonder if two years of treatment is truly necessary. Two years of therapy can be a significant burden for patients, who must take time off from work every three to four weeks for treatment. There's no clear biological or scientific rationale for a two-year duration; some patients respond to treatment after only a few doses, and the effects of immunotherapy can even persist after treatment stops. This was the basis for the DANTE trial: to determine if two years of treatment is truly needed, or if one year of therapy could be sufficient.

The study was primarily conducted in the United Kingdom, with an initial goal of enrolling 1,200 patients. Unfortunately, the study had to close after several years, accruing only 166 patients in total. Therefore, the study was considered underpowered, meaning it didn't reach the target number of patients needed to statistically prove if one year versus two years yielded the same or better results. The study's goal was to prove that one year was non-inferior to two years.

What the study did find was that, overall, one year of treatment was not statistically inferior to two years of therapy in terms of progression-free survival. This suggests that we could potentially reduce treatment to one year instead of two. However, due to the study being underpowered, the investigators concluded that the standard of care should remain a minimum of two years of immunotherapy for patients with advanced-stage melanoma.

One crucial question the study did not fully answer is the overall survival outcomes between two years versus one year, and this remains an unanswered question. Nonetheless, other studies are currently underway that are exploring the role of giving less therapy based on how patients respond to treatment. Therefore, this is neither the first nor the last time we'll hear about a study investigating the proper duration of immunotherapy for patients with advanced-stage melanoma.

What were some of the updates in adjuvant treatment for patients with stage 3 or 4 melanoma, particularly from the RELATIVITY study?

Absolutely. At ASCO this year, investigators presented data from the RELATIVITY-098 trial. This particular study aimed to look at the role of giving Opdivo (nivolumab) plus Opdualag (relatlimab) in the adjuvant setting, specifically after surgical resection of stage 3 or 4 melanoma.

To give you a little background on treating melanoma after surgery, the current standard of care for resected high-risk stage 2 or stage 3 melanoma offers two main options. Patients can receive anti-PD-1 therapy, like Opdivo or Keytruda (pembrolizumab), after surgery. Alternatively, if a patient has a BRAF V600 mutation, they can use BRAF/MEK targeted therapy. While these FDA-approved drugs have been shown to reduce recurrence, which is excellent, not all patients benefit from adjuvant anti-PD-1 or BRAF/MEK targeted therapy. So, researchers are exploring new ways to help prevent recurrence.

What are some of the recent efforts to explore new adjuvant treatment strategies for patients with stage 3 or 4 melanoma?

[Because] researchers are exploring new ways to help prevent recurrence, we asked: where do we look for drug opportunities to reduce recurrence? We currently have FDA approval for Opdivo plus Opdualag for unresectable stage 3 and 4 melanoma. This was FDA approved back in 2022 and has been shown to improve response rates, progression-free survival, and overall survival in patients with advanced stage melanoma.

The investigators of the RELATIVITY-098 trial wanted to see if we could use Opdivo plus Opdualag in the adjuvant setting, after surgical resection of stage 3 and 4 melanoma. This was a phase 3 study where they looked at half of the patients who received Opdivo plus Opdualag after surgery, and the other half of patients received Opdivo by itself, which is the standard of care arm.

What they found in the study was that there was actually no difference in terms of recurrence-free survival between the two arms. This was a bit of a surprise because we know there's efficacy and benefit to using Opdivo plus Opdualag in the unresectable setting. However, we didn't really see the benefit of two drugs versus one drug in this particular phase 3 trial. The investigators and researchers tried to break it down to see if there was a particular group of patients that might benefit from two drugs versus one, but they didn't find a specific subgroup.

From the findings of this overall study, the standard of care still remains that for patients after resection of stage 2, stage 3, or stage 4 melanoma, anti-PD-1 monotherapy should still be the standard of care, rather than a two-drug immunotherapy regimen.

Transcript has been edited for clarity and conciseness

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