Key Skin Cancer Treatment Updates From 2025 and What is Still to Come

During the first half of 2025, several key updates have been shared on evolving treatment strategies for patients with high-risk cutaneous squamous cell carcinoma and melanoma, two distinct forms of skin cancer.

“Many findings [in skin cancer that were shared] this year were really just affirming what we've been doing for the past few years,” Dr. Vincent Ma, a faculty member in the Division of Hematology, Medical Oncology and Palliative Care at the University of Wisconsin, said of these treatment updates in an interview with CURE.

In the interview, he discussed some of the most notable updates so far this year regarding treatment strategies for patients with high-risk cutaneous squamous cell carcinoma, as well as highlighted how to reduce the risk of skin cancer recurrence in patients with this disease.

Moreover, Ma, who 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, shared more on the this topic in another article with CURE.

CURE: What have been some of the most notable updates so far this year regarding treatment strategies for patients with high-risk cutaneous squamous cell carcinoma?

Ma: At the 2025 ASCO Annual Meeting this year, we actually had some very interesting updates about how we think about treating patients with high-risk cutaneous squamous cell carcinoma. Squamous cell carcinoma of the skin is the second most common skin cancer in the United States, and we know that a good proportion of patients actually have high-risk disease.

High-risk means a very high risk of coming back after surgery. The current standard of care for patients with high-risk squamous cell carcinoma of the skin is surgery followed by radiation therapy. But what we really don't know in this particular space is if there's any benefit to giving any treatments after surgery and after radiation to prevent the skin cancer from coming back. We know that about 30% of patients at five years with high-risk squamous cell skin cancer actually experience recurrence. So, [we ask ourselves]: is there a way that we can prevent the recurrence of the skin cancer?

What potential approaches are being explored to reduce the risk of skin cancer recurrence in patients with high-risk squamous cell carcinoma?

There were actually two trials that were well highlighted this year to look and answer that particular question. One of them is called the KEYNOTE-630 trial, and the other one is called the C-POST trial. Both of those trials are looking to see if there is a role for giving immunotherapy, specifically anti-PD-1 therapy, after surgery and after radiation in order to prevent recurrence of squamous cell skin cancer. Just a little background on that: anti-PD-1 therapy is actually FDA approved right now to treat advanced stage squamous cell skin cancer. That means skin cancer that has spread and is no longer eligible for surgery. We're, of course, trying to see if we can bring that into the adjuvant setting to help prevent recurrence.

KEYNOTE-630 was a trial that looked at giving adjuvant Keytruda (pembrolizumab), which is anti-PD-1 therapy. They looked at giving it for a full year duration for half the patients that were studied, and the other half of the patients received placebo. What they ended up finding was that there was no statistical difference in terms of recurrence-free survival between the two arms. So there was no difference in terms of recurrence between those who got adjuvant Keytruda for one year versus placebo. That was an interesting finding from there.

In contrast, when we looked at the C-POST study, we actually discovered that those patients who, for example, got anti-PD-1 therapy — in the case of the C-POST study, it was Libtayo (cemiplimab) — and they also compared it to an arm of patients who got placebo, they actually found statistical significance in terms of disease recurrence. It was very interesting to kind of see that two studies, you know, studied a similar drug, which is anti-PD-1 therapy, and they both had a similar comparison arm, which is placebo.

One study in particular, which was the C-POST study, had a disease-free survival benefit. It's very interesting to note that. What was also very interesting between the two studies was that there were slight differences in terms of nuances between the patient population that was analyzed, as well as the endpoints that they were analyzing.

Overall, I think the conclusion from the study is that because we saw a disease-free survival benefit from patients who received adjuvant Libtayo for one year in the C-POST study, it is likely to eventually become standard of care in the future for patients who have high-risk squamous cell carcinoma of the skin following surgery and radiation.

To close, what should patients with melanoma or high-risk cutaneous squamous cell carcinoma take away from today’s conversation?

Many findings [in skin cancer that were shared] this year were really just affirming what we've been doing for the past few years. This includes, first, for patients who have advanced stage melanoma, the standard of care should primarily be immunotherapy in the first-line setting. Updates were presented from the DREAMseq study, which is a landmark study that showed that for patients with unresectable BRAF-mutated melanoma, the preference should be immunotherapy first, rather than BRAF/MEK targeted therapy. The five-year follow-up data was presented at ASCO this year, and what they showed and confirmed is that patients treated with immunotherapy had a longer duration of benefit from treatment, had less metastases to the brain, and starting with immunotherapy allows for a better response to later lines of treatment if their melanoma progresses.

Another important point is the long-term follow-up from TIL therapy. TIL therapy was FDA approved in 2024, and the five-year follow-up data was presented. To provide some background on TIL therapy, it is FDA approved for advanced stage melanoma patients whose disease has progressed on standard immunotherapy and targeted therapy treatment. What was presented at ASCO this year was the five-year follow-up data, which showed that the long-term benefit from TIL therapy for those who responded continues to remain significant. That was a major highlight from ASCO this year.

Another important highlight overall from the RELATIVITY-098 trial is that anti-PD-1 monotherapy following resection remains the standard of care for adjuvant treatment of melanoma. The final highlight is that continuing anti-PD-1 based therapy for at least two years continues to remain the standard of care for first-line treatment of advanced stage melanoma.

Finally, that adjuvant treatment with anti-PD-1 therapy with Libtayo is likely to become a standard of care option for specific high-risk cutaneous squamous cell carcinoma patients.

Transcript has been edited for clarity and conciseness

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.