P156 Neoadjuvant immunotherapy for advanced melanoma: a clinical audit of pathological response and toxicity

Abstract Outcomes associated with stage III and above melanoma are poor. The SWOG S1801 trial compared neoadjuvant and adjuvant pembrolizumab in advanced melanoma and found better event-free survival in the former (Patel SP, Othus M, Chen Y et al. Neoadjuvant–adjuvant or adjuvant-only pembrolizumab in advanced melanoma. N Engl J Med 2023; 388: 813–23). The OpACIN-neo trial identified a dose of neoadjuvant ipilimumab plus nivolumab that induced a response with acceptable adverse events [Rozeman EA, Menzies AM, van Akkooi ACJ et al. Identification of the optimal combination dosing schedule of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (OpACIN-neo): a multicentre, phase 2, randomised, controlled trial. Lancet Oncol 2019; 20: 948–60). The aim of our audit was to assess patients in our centre over 12 months for pathological response to neoadjuvant immunotherapy and any associated toxicity. Patients with melanoma who had received at least one neoadjuvant immunotherapy treatment for their disease were selected. Data were collected by manually reviewing their medical health records, including both their paper file and electronic databases. Information collected included age, sex, Eastern Cooperative Oncology Group status, subtype, primary site, mutation status, blood results, number of cycles received, adverse events, date of surgery, pathological response and date of death. Data from 19 patients were collected, including 14 with nodular melanoma, two with superficial spreading and nodular melanoma, and two with superficial spreading melanoma. Stages ranged from III to IV. Fourteen received pembrolizumab and four received ipilimumab plus nivolumab, with all patients receiving between two and four cycles. Adverse events included dermatitis, colitis, hepatitis, hyperthyroidism, arthritis and neurovasculitis. Fifteen patients underwent surgery, with three patients excluded due to progression of disease and one surgery pending. One patient had pathological complete response, six patients had pathological partial response, and eight patients had pathological nonresponse. Our findings indicate similar numbers of partial and nonresponse to treatment, along with a broad spectrum of associated toxicities. One-half (50%, n = 4) of patients receiving ipilimumab plus nivolumab experienced adverse events. These results differ from the more promising findings in the SWOG S1801 and OpACIN-neo trials, which followed 313 and 86 eligible patients, respectively. Further patient enrolment is needed to accurately assess the risk–benefit profile of neoadjuvant immunotherapy in melanoma management.