What Libtayo Means for High-Risk Cutaneous Squamous Cell Carcinoma

Dr. Vishal A. Patel, a Mohs surgeon and dermato-oncologist at George Washington University, explains that Libtayo (cemiplimab-rwlc)’s new FDA approval provides patients with high-risk cutaneous squamous cell carcinoma with an effective adjuvant option.

For those who have had surgery and radiation but remain at significant risk for recurrence, this immunotherapy reduced recurrence risk by 68% in the C-POST trial, including both local and distant cancer.

Adjuvant Libtayo is given after surgery and radiation to help prevent cancer from returning rather than treating existing tumors. Its safety profile in this setting is consistent with what is known for Libtayo in advanced cancers. The most common side effects, occurring in 10% or more of patients and with a difference of 3% or more compared to placebo, included rash, itching and hypothyroidism. Serious side effects occurred in 18% of patients, with pneumonia, rash, diarrhea, adrenal insufficiency and arrhythmia affecting 1% to 1.5% of patients. Only 10% of patients stopped therapy due to side effects, while about 20% needed temporary breaks.

While patients with autoimmune disease or prior transplants were excluded, this approval significantly expands post-surgical options for high-risk patients, allowing clinicians to tailor therapy based on tumor risk.

CURE: For patients who have already undergone surgery and radiation for high-risk cutaneous squamous cell carcinoma, what does this new approval of Libtayo mean in practical terms?

Patel: What this means is that for patients at the highest risk for poor outcomes — those who have already had surgery and whose risk factors are particularly concerning enough that we recommended radiation, but we were not confident that radiation alone would prevent recurrence — we now have strong data and approval to use a systemic immunotherapy to help prevent those outcomes.

In the clinical trial, this therapy reduced the risk of recurrence by about 68%, which, in context, is as good as it gets in the adjuvant setting. Compared to trials in melanoma or other cancers, this is a very impressive risk reduction for these high-risk patients.

Can you explain what the C-POST trial found regarding how well Libtayo worked to prevent cancer from coming back?

The headline is that it was a blockbuster result. The trial was structured in a very stringent way, comparing placebo to therapy after surgery and radiation, and it specifically included tumors with very high recurrence risk — 30% to 40%, depending on the risk factors. Libtayo reduced the risk of recurrence by 68%. Importantly, this reduction applied both to local recurrence and distant metastases, showing that in the right patients, this therapy is not only effective but robust, giving us confidence it can help prevent recurrence when added as adjuvant immunotherapy.

How does adjuvant or post-surgical treatment with Libtayo differ from using it for advanced or metastatic disease?

Oncology has various terms, including salvage or metastatic therapy, which was the original approval for Libtayo in situations where surgery and radiation are no longer options. In those scenarios, immunotherapy can reduce or clear tumors.

Adjuvant therapy takes that a step earlier: patients undergo surgery and radiation with curative intent, but the chance of cure is relatively low, so additional systemic therapy helps prevent recurrence. Adjuvant therapy is a prevention approach, whereas metastatic or salvage therapy is a treatment approach when other options are no longer viable.

What types of side effects should patients be aware of with Libtayo, and how are they typically managed?

The C-POST trial showed no new side effects beyond what is already known for Libtayo, an anti-PD-1 immunotherapy. Because it activates the immune system to attack cancer, sometimes healthy tissues like the liver or bowel can be affected. Management is well established, and weighing risks versus benefits is essential. In the trial, only 10% of patients had to stop the medication due to side effects, while about 20% had temporary breaks. Overall, it is generally well tolerated and significantly better tolerated than chemotherapy, which was often the only alternative.

Why were certain patients, like those with autoimmune disease or prior transplants, excluded from the study, and what does that mean for people in those groups?

These patients were excluded to keep the trial safe and clean.

Activating the immune system in someone with an autoimmune condition or a transplant could worsen disease or risk the transplanted organ. These groups often face the most challenging skin cancers, and research is ongoing to determine how to treat them safely, but they were not included in this study.

How do you see this approval shaping the standard of care for people with high-risk cutaneous squamous cell carcinoma?

This approval adds depth to how we approach cutaneous squamous cell carcinoma at all stages. For high-risk patients, rather than waiting for a devastating recurrence — especially in older, more frail patients — we can evaluate tumor risk post-surgery and consider adjuvant therapy when tolerated. This gives us more options and significantly changes how we think about treatment based on tumor risk.

Transcript has been edited for clarity and conciseness.

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