Proffered paper session melanoma

During ESMO 2025, Prof Bart Neyns, Medical Oncologist at the University Hospital Brussels, chaired the Proffered Paper Session on melanoma and skin cancer. In this video, he provides a comprehensive overview of the key studies presented, outlining the most significant findings and their implications for clinical practice.

A major focus during the session was once again the role of neoadjuvant immunotherapy in patients with resectable, macrometastatic melanoma. Until recently, the standard of care for these patients consisted of surgical resection followed by one year of adjuvant anti–PD-1 monotherapy. Two pivotal randomized trials, the NADINA trial and the SWOG S1801 trial, have challenged this paradigm by introducing immunotherapy in the neoadjuvant setting.

The NADINA trial investigated a short course of combination immunotherapy consisting of ipilimumab at one milligram per kilogram together with nivolumab at three milligrams per kilogram administered prior to surgery. Importantly, the design of this study incorporated pathological response as a surrogate marker to tailor subsequent adjuvant therapy. Patients achieving a major pathological response were able to discontinue treatment. This strategy was based on prior evidence demonstrating excellent outcomes for such responders, a finding now confirmed with the most recent data. Conversely, patients without a major pathological response were stratified by BRAF status, receiving either BRAF/MEK inhibition for one year if mutated, or anti–PD-1 monotherapy if wild-type.¹ The SWOG S1801 trial employed a different approach, relying exclusively on anti–PD-1 monotherapy with pembrolizumab. Patients either received the agent for one year in the adjuvant setting or underwent three cycles of neoadjuvant pembrolizumab followed by surgery and then continuation of pembrolizumab for one year.²

Updated results of these trials confirmed impressive improvements in event-free survival with both neoadjuvant approaches. At the two-year landmark, the SWOG study demonstrated an approximate 15% absolute improvement in EFS, while the NADINA trial reported a delta closer to 20%.1,2 These data have already led to the incorporation of neoadjuvant therapy into the most recent ESMO guidelines, establishing it as a new standard of care.

For Prof Neyns, choosing between the two strategies requires careful discussion with patients. NADINA offers the possibility to stop treatment after only two cycles in the majority of patients, as roughly 60% achieve a major pathological response. However, this advantage must be weighed against the higher incidence of severe immune-related adverse events associated with the combination regimen, with approximately 7.5% of patients developing lifelong adrenal insufficiency. In contrast, the SWOG S1801 regimen exposes patients only to anti–PD-1 monotherapy and carries a lower toxicity risk, making it attractive for those in whom safety is a particular concern.

Beyond the neoadjuvant trials, the Dutch Safe Stop trial examined elective discontinuation of anti–PD-1 therapy in patients with unresectable metastatic melanoma who achieved either a complete or partial responses. Results suggested excellent outcomes for patients who stopped therapy in the absence of toxicity or progression.³ Nevertheless, Prof Neyns recommends to remain cautious, preferring individualized decision-making. Personally, he prefers to continue therapy for at least one year, particularly in partial responders or those with residual PET activity.

Finally, results were presented from a phase 3 study evaluating pembrolizumab in combination with IO102-IO103, an investigational immune-modulatory therapeutic cancer vaccine designed to stimulate activation and expansion of T cells against IDO1- and PD-L1-expressing cells, thereby targeting both tumour and immune-suppressive cells in the microenvironment.⁴ Despite earlier enthusiasm from phase 2 data, the trial failed to meet its primary endpoint of progression-free survival. While a numerical advantage was observed in the Kaplan–Meier curves, this difference was not statistically significant and did not translate into a benefit in overall survival. The study must therefore be considered negative. Further exploration may clarify the biological underpinnings of the PFS signal, but for now the approach remains investigational.