Trial Updates in Stage III Melanoma Solidify the Neoadjuvant Use of Immunotherapy as the Current Standard of Care
Source: The Asco Post, October 2024
Neoadjuvant therapy for patients with resectable stage III melanoma has recently emerged as a better approach than resection plus adjuvant therapy. At the European Society for Medical Oncology (ESMO) Congress 2024, updates of pivotal neoadjuvant studies demonstrated the long-standing benefit of this approach and validated it as the current standard of care.1,2 The new findings also cement pathologic complete response as the best means of projecting outcomes.
Georgina V. Long, PhD, MBBS, of the Melanoma Institute Australia, University of Sydney Royal North Shore and Mater Hospitals, put the treatment benefit seen with neoadjuvant therapy into context. She noted the remarkable benefits achieved to date with adjuvant anti–PD-1 monotherapy (pembrolizumab and nivolumab), which render half of the patients recurrence-free at 5 years. Now, neoadjuvant administration of checkpoint inhibitors has nudged out using these agents only in the adjuvant setting in resectable macroscopic stage III melanoma, as demonstrated by the randomized phase II SWOG S1801 study (single-agent pembrolizumab followed by adjuvant pembrolizumab)3 and the randomized phase III NADINA study (ipilimumab plus nivolumab with response-adapted adjuvant therapy),4 where risk reductions of 42% and 68%, respectively, were achieved compared with the standard adjuvant anti–PD-1 monotherapy.
NADINA Trial of Ipilimumab Plus Nivolumab
The NADINA trial included 423 patients, randomly assigned 1:1 to either ipilimumab plus nivolumab in the neoadjuvant setting or standard nivolumab in the adjuvant setting after resection. Those in the neoadjuvant arm received two courses of ipilimumab plus nivolumab followed by resection; patients not achieving a major pathologic response received adjuvant nivolumab if BRAF wild-type or dabrafenib plus trametinib if BRAF-mutated. The control arm underwent resection followed by adjuvant nivolumab. Radiotherapy was given if indicated.