New drugs non-melanoma

Over the last decade, several new therapies have entered the treatment armamentarium for patients with melanoma. Building on the success that was obtained in this setting, these therapies are now increasingly being used in the treatment of patients with non-melanoma skin cancer. During EADV 2024, Prof Dr Lidija Kandolf-Sekulovic, dermatologist at the Military Medicine Academy in Belgrade (Serbia) gave an overview of emerging therapies for patients with cutaneous squamous cell carcinoma (CSCC), basal cell carcinoma (BCC) and Merkel cell carcinoma (MCC).¹

The high mutational burden and increased risk of CSCC in patients under immunosuppression formed the rationale to evaluate immune checkpoint inhibitors (ICIs) in this setting. Clinical studies with cemiplimab, pembrolizumab and to a lesser extent also nivolumab indicate an objective response rate (ORR) of about 50% in patients with advanced CSCC. Interestingly, recent evidence suggests that the EGFR tyrosine kinase inhibitor (TKI) cetuximab immediately after failure of an ICI yields particularly fast and durable responses. Other innovative strategies that are explored in CSCC consist of dual ICI therapy for patients with advanced disease, the use of ICIs in the neoadjuvant setting and the use of intratumoral therapies such as RP1 or TLR9 antagonists.

For patients with advanced BCC, the current standard of care in first line consists of inhibitors of the hedgehog signaling pathway. In 2^nd line, ICI therapy is able to induce durable responses in a substantial proportion of patients. For the moment, several studies are evaluating whether a combination of these two treatment strategies leads to a synergistic effect. As for CSCC, studies are also underway evaluating ICIs in the neoadjuvant setting while other trials are looking into the incorporation of intratumoral therapies for these patients.

For patients with advanced MCC, anti-PD-(L)1 antibodies are the current standard of care in first line, with an ORR ranging from 33% to 68%. To further boost this response rate, studies are evaluating ICI doublets or even triplets. With respect to the latter, Prof Kandolf specifically mentioned a study evaluating a combination of an anti-PD1, anti-LAG3 and anti-TIM3 in patients with MCC. Also in MCC studies are evaluating neoadjuvant ICI therapy and are looking into the potential added value of intratumoral therapies.