Squamous cell carcinoma + rare tumours

During EADO 2025, Dr Celine Jacobs, a medical oncologist at the University Hospital in Ghent, discussed three studies presented during the session on squamous cell carcinoma (SCC) and rare tumours.

The first study was the phase 1b/2 ARTACUS trial investigating RP1, an oncolytic immunotherapy, in patients with advanced cutaneous carcinomas who had previously undergone solid organ transplantation. These patients represent a unique and high-risk group, as skin cancer is the most common malignancy post-transplant, and standard immunotherapies carry a significant risk of organ rejection. In this trial, RP1 was administered through direct injection into visible lesions, including cutaneous, subcutaneous, and nodal lesions. Most patients had CSCC, with some cases of Merkel cell carcinoma. The cohort included recipients of lung, kidney, and liver transplants.

The treatment demonstrated encouraging results, with an overall response rate exceeding 30% and a complete response rate above 20%. Notably, no instances of organ rejection were observed, and adverse events were generally mild. The study also reported durable responses, although in some cases, response times were delayed, possibly due to ongoing immunosuppression. These findings suggest that RP1 may offer a safe and effective treatment option for this patient population, where standard checkpoint inhibitors are not viable. The results support further investigation in larger phase 2 or 3 trials.

The second study evaluated the use of neoadjuvant cemiplimab in patients with resectable CSCC, stages 2 to 4. Initial findings from the study, published in 2022, showed that over half of the patients achieved a complete pathological response after two to four cycles of treatment, while an additional 10% -13% had a major pathological response. At the time the study was designed, adjuvant therapy following surgery was permitted at the discretion of the physician. Today, with data from trials like NADINA in melanoma, treatment strategies may be different, favouring treatment cessation after major or complete pathological response.

With follow-up now extending to 2-2.5 years, long-term outcomes remain favourable. Among patients who had a complete or a major pathological response, relapse rates were extremely low. Conversely, non-responders to neoadjuvant treatment were more likely to relapse. While some variability exists due to non-standardised adjuvant treatment regimens, the data reaffirms the safety and efficacy of cemiplimab in this setting. Future phase 3 trials comparing this approach to standard surgery or radiotherapy will be essential for refining treatment protocols, particularly given the typically older age of the patient population.

The third study was a retrospective analysis examining long-term recurrence and survival in patients with CSCC who had undergone primary resection. The focus was on surgical margin status and its impact on outcomes over a nearly seven-year follow-up period. Patients were grouped based on their resection margins: clear margins (all >1 mm), close margins (at least one <1 mm), and involved margins (tumour present at the edge). A multidisciplinary tumour board reviewed all cases, and decisions regarding additional local treatment were made accordingly. No patients received systemic therapy.

The analysis revealed similar and favourable outcomes for patients with clear and close margins, characterised by low local and regional recurrence rates in both groups. In contrast, patients with involved margins had significantly higher relapse rates, confirming the need for further local treatment in this subgroup. These results carry important clinical implications, particularly in cases where wider margins are not feasible due to anatomical or cosmetic constraints. The data support a more tailored approach: patients with close margins may not require aggressive intervention if carefully followed, while those with involved margins clearly benefit from additional therapy.