The C-POST trial was a phase III adjuvant trial in patients at high risk of recurrence of cutaneous SCC after surgery and radiotherapy, randomising between cemiplimab and placebo. The background to this is that although cutaneous squamous cell cancers are very common and the majority are cured by surgery, there remains a subset of patients who remain at high risk despite surgery and radiotherapy.
Previously there were no effective adjuvant systemic therapies. We know that the anti-PD-1 targeting drug cemiplimab is standard of care in patients with more advanced or metastatic cutaneous SCC, where it achieves a response rate of 47% with responses that can be durable. We really wanted to test if using it as an adjuvant treatment in earlier stage of disease with patients at high risk of recurrence could improve the outcomes and prevent recurrence in these patients.
What was the methodology, and what were the findings?
The C-POST phase III trial was a randomised phase III trial in patients at high risk of recurrence for cutaneous SCC. Patients were randomised in a double-blind placebo-controlled fashion after surgery and radiotherapy to either cemiplimab or placebo. Patients were selected based on high-risk criteria, either nodal or non-nodal criteria, that put them at risk of recurrence in the order of 45% risk.
There were 415 patients randomised, they were well-balanced between the two arms. Patients, as you’d expect for this disease, were elderly – median age was 71. They were predominantly male, white, and had head and neck primaries, which is what we’d expect for this disease. About 60% of patients had what we call high-risk nodal criteria, which means they had large nodes of extracapsular extension, or a large number of lymph nodes.
The key finding from the study and the primary endpoint was disease free survival. We showed that cemiplimab compared to placebo improved disease free survival with a hazard ratio of 0.32, so 68% reduction, p-value less than 0.0001. In the placebo arm there was a marked falloff in disease free survival in the first 12 months, consistent with what we know about these high-risk patients. The median disease free survival was not reached in the cemiplimab arm, and it was 49 months in the placebo arm. At two years, the disease free survival in the cemiplimab arm was 87%, whilst in the placebo it was only 64%.
We saw benefit in all pre-specified subgroups, including patients that had nodal high-risk criteria, non-nodal high-risk criteria, and irrespective of PD-L1 expression. This decrease in occurrences was due to both a decrease in local regional recurrences, with an 80% reduction, and also a decrease in distant metastases at 65% reduction.
Safety was good, it was well-tolerated, it was as one would expect for an anti-PD1 agent with no additional toxicities. Quality of life was maintained during the treatment with no significant differences between the arms.
What are the clinical implications of these findings?
This trial demonstrates that cemiplimab is the first adjuvant treatment to demonstrate a statistically significant and clinically meaningful improvement in disease free survival. It provides an option for these patients to prevent recurrence. As many of the recurrences are local regional, they can be associated with considerable morbidity, so it may be an advantage for many patients to have adjuvant cemiplimab to prevent these recurrences from occurring.
