At the European Society for Medical Oncology (ESMO) Congress 2023, new findings are being presented in cutaneous squamous cell carcinoma, late-stage melanoma, and refractory melanoma brain metastases.
Presurgical Immunotherapy in Advanced Operable Cutaneous Squamous Cell Carcinoma
Patients with cutaneous squamous cell carcinoma—the second-most common form of skin cancer—typically present with early-stage disease that can be treated with surgery alone, though a subset with more advanced disease will require radiation in addition to surgery. In a 1-year follow-up to a multicenter phase II study led by Neil D. Gross, MD—first presented at the ESMO Congress 2022—neoadjuvant immunotherapy given to patients with advanced resectable cutaneous squamous cell carcinoma demonstrated favorable survival outcomes, with a median follow-up duration of 18.7 months (Abstract 1088MO).
The study included 79 participants treated with neoadjuvant cemiplimab followed by curative-intent surgery. Based on treatment response, patients were offered up to 48 weeks of adjuvant cemiplimab, radiation therapy, or observation only. Estimated 12-month event-free survival was 89%. Notably, none of the 40 patients with a pathologic complete response experienced recurrence. The results indicate that neoadjuvant cemiplimab followed by surgery is a viable treatment option for advanced, operable cutaneous squamous cell carcinoma. A phase III trial is planned to test this novel approach.
Perioperative Immunotherapy in Patients With Late-Stage Melanoma
Patients with advanced melanoma face a significant risk of relapse even after surgery. Adding immunotherapy to surgery is considered more effective than surgery alone. In the SWOG S1801 phase II study—results of which were presented at the ESMO Congress 2022—researchers led by Sapna Patel, MD, demonstrated perioperative immunotherapy resulted in better survival than adjuvant immunotherapy alone.
A follow-up analysis, presented at the ESMO Congress 2023, found more than half of the participants who received perioperative immunotherapy had a major pathologic response, meaning there was < 10% remaining viable tumor after three doses of neoadjuvant pembrolizumab (Abstract LBA48). These data suggest perioperative pembrolizumab results in favorable tumor changes in a majority of patients.
Triplet Combination in Patients With Refractory Melanoma Brain Metastases
While many patients with melanoma brain metastases respond well to immune checkpoint blockade, many fail to respond or subsequently develop resistance, leaving them with limited systemic treatment options and a poor prognosis. In a phase II study, a research team led by Elizabeth Burton, PhD, examined the safety and efficacy of atezolizumab, bevacizumab, and cobimetinib in 20 patients with treatment-refractory melanoma brain metastases (Abstract 1085O).
The intracranial response rate and intracranial benefit rate were 39% and 56%, respectively. Safety was consistent with expectations, with 18 patients experiencing treatment-related adverse events and 7 (35%) experiencing grade 3/4 treatment-related adverse events. Although median progression-free survival was 2.7 months, median overall survival was 9.3 months. Seven patients (35%) received treatment beyond disease progression, including stereotactic radiosurgery, after evaluation by The University of Texas MD Anderson Cancer Center's multidisciplinary Brain Metastasis Clinic. These results, which highlight the tolerability of the combination, merit further clinical evaluation and underscore the importance of integrating multidisciplinary care into the evaluation of novel therapeutic strategies in this patient population.
Disclosure: For full disclosures of the study authors, visit cslide.ctimeetingtech.com/esmo2023.
