Neoadjuvant cemiplimab for resectable stage II to IV skin squamous cell carcinoma

The large, deeply invasive cutaneous squamous cell carcinomas that arise on the face and scalp of older people are curable by surgery, but the surgery can be disfiguring or can cost an eye. This trial asked whether shrinking them first with a PD-1 antibody would change what had to be removed.

Seventy-nine patients with resectable stage II to IV disease received up to four doses of cemiplimab 350 mg every three weeks and then went to surgery. The primary endpoint was a pathological complete response, meaning no viable tumour cells anywhere in the surgical specimen on independent central review, with a null hypothesis of 25 per cent.

A pathological complete response was found in 40 of 79 patients (51 per cent, 95 per cent confidence interval 39 to 62) and a pathological major response, defined as viable tumour making up 10 per cent or less of the specimen, in a further 10 (13 per cent, 6 to 22). Almost two-thirds of the specimens therefore contained little or no living cancer. Imaging responses, at 68 per cent (57 to 78), understated the pathological result, which is the usual pattern with immunotherapy and is the reason the pathologist rather than the scanner decides this endpoint. Adverse events of any grade during the study occurred in 69 patients (87 per cent) and grade 3 or higher in 14 (18 per cent).

What the trial does not yet answer is whether the surgery can be reduced, or omitted, on the strength of the response. It was designed with surgery for everybody, so the pathological complete responses were resected rather than watched. That is the next question, and it is the same question being asked after neoadjuvant immunotherapy in rectal and in bladder cancer.