Previous attempts at neoadjuvant therapy weren’t particularly effective. Although physicians in the 1970s and 1980s tried shrinking tumors with chemotherapy prior to surgery, neoadjuvant chemotherapy “never really caught on for this type of cancer,” Dr. Gross said. Intra-arterial chemotherapy has been investigated as a neoadjuvant therapy for head and neck squamous cell carcinoma, but to date, “no obvious evidence for positive responses has been reported,” according to an article published in Frontiers of Oncology (2018;8:79).
Explore This IssueApril 2023
Immunotherapy appears to be a game changer. Skin cancers are particularly sensitive to immunotherapy because most are caused by UV damage from the sun, which creates many DNA mutations in cancerous tumors. Administering immunotherapy in the neoadjuvant setting may be especially beneficial, because “when the bulk of the tumor is still present, a more profound and broader immune response can be induced,” said Nader Sadeghi, MD, professor and chair of the department of otolaryngology–head and neck surgery at McGill University Health Center in Montreal and director of the McGill Head and Neck Cancer Program. “This is because the cancerous tumor is composed of many heterogeneous colonies of cells, and broader antigen presentation from tumor cells can induce more robust tumor-specific T-cell response.” The hope, he said, is that this immune effect continues after surgery as well.
Though long-term progression-free survival data are not yet available, as neoadjuvant treatment of cutaneous squamous cell carcinoma is still a relatively novel approach, research to date suggests that neoadjuvant immunotherapy may indeed lead to good outcomes, at least for some patients.
“We now have long-term survival data from the 20 patients who participated in the initial pilot trial, and their responses have been very durable,” Dr. Gross said. “Every single one of the 15 patients who experienced a response to immunotherapy has remained disease-free for an average of 42 months.”
Neoadjuvant Immunotherapy for Advanced Cutaneous Squamous Cell Carcinoma
The first pilot study of neoadjuvant immunotherapy for advanced, resectable squamous cell carcinoma used cemiplimab. Patients received two cycles of intravenous cemiplimab every three weeks before surgical resection. Only two doses were given, because physicians (and patients) didn’t want to delay surgery any longer, according to Dr. Gross.
The initial plan called for all enrolled patients to undergo both surgery and adjuvant radiation. “Given the dramatic pathologic responses to neoadjuvant immunotherapy, however, the majority of patients (60%) did not receive adjuvant radiotherapy … None of these patients developed recurrence.” (Clin Cancer Res. 2021;27:4557–4565).