Neoadjuvant cemiplimab exhibited high therapeutic activity in adults with resectable cutaneous squamous-cell carcinoma, according to data from a phase 2, confirmatory, multicenter, nonrandomized study published in The New England Journal of Medicine.
Investigators included adults with resectable stage II, III, or IV (M0) cutaneous squamous cell carcinoma for which primary surgery would be recommended in routine clinical practice. All patients had adequate organ function, at least 1 measurable lesion, and an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1, with higher scores indicating greater disability. This article reported the first part of the study, which evaluated cemiplimab as neoadjuvant therapy before surgery with curative intent.
Patients received 350 mg IV cemiplimab every 3 weeks for as many as 4 doses during a 12-week period, or until the occurrence of unacceptable toxic effects, disease progression, or consent withdrawal. Investigators performed imaging (CT or MRI) of externally visible lesions at baseline, week 6 (before the third dose), and week 12 (before surgery). The primary endpoint was a pathological complete response, defined as “the absence of viable tumor cells in the surgical specimen obtained after treatment.”
There were 79 patients included in the study with a median age of 73 years (range, 24-93), and 85% were men. There were 9 patients who did not undergo surgery within the acceptable timeframe and therefore had no pathological evaluation. The most common tumor site was the head and neck region, and most patients had stage III or IV disease. Median follow-up from the first dose of cemiplimab to data-cutoff date was 9.7 months (range, 1.3-19.6).
There was a pathological complete response in 51% of patients (95% CI, 39-62%), ruling out the null hypothesis that a pathological complete response would be seen in 25% of patients. There was an objective response on imaging after treatment with cemiplimab, with 5 patients having complete response and 49 having partial response. Most patients with a pathological complete response did not have a complete response on preoperative imaging.
Adverse events during the study period occurred in 87% of patients, the most common being fatigue, diarrhea, nausea, and maculopapular rash. Investigators determined 72% of adverse events to be related to treatment, including grade 3 immune-related adverse events. There were 4 fatal adverse events during the study period. One patient, a 93-year-old woman, experienced a fatal exacerbation of congestive heart failure after 2 doses of cemiplimab, which was considered to be possibly related to the treatment.
The study was limited by the absence of a control group and relatively short median follow-up time, and the discordance between patients with complete response on imaging and complete pathological response.
“The potential for function-preserving surgery, together with the high frequency of a pathological complete response, supports the use of neoadjuvant therapy with cemiplimab in this patient population,” the study authors wrote.
Disclosure: This research was supported by Regeneron and Sanofi. Please see the original reference for a full list of disclosures.
Gross ND, Miller DM, Khushalani NI, et al. Neoadjuvant cemiplimab for stage II to IV cutaneous squamous cell carcinoma. N Engl J Med. Published online October 27, 2022. doi:10.1056/NEJMoa2209813