ASCO24: Opdivo, Yervoy pre-surgery sets new standard in stage III melanoma

Administering immunotherapy with Bristol Myers Squibb's Opdivo (nivolumab) and Yervoy (ipilimumab) to patients with stage III melanoma before surgery demonstrates more favorable outcomes compared to the current practice of post-surgery immunotherapy. This conclusion emerged from the Phase III NADINA trial, results of which were shared at the American Society of Clinical Oncology (ASCO) annual meeting.

The trial involved 423 stage III melanoma patients who either received the combination of Opdivo and Yervoy before their lymph nodes were surgically removed or followed the standard procedure of receiving Opdivo after lymph node removal. For those who did not achieve a major pathological response—defined as the destruction of 90% or more of the tumor cells in the surgically removed lymph nodes—additional treatment with Opdivo or targeted therapies for tumors with a BRAF gene mutation was administered.

The results revealed that administering Opdivo and Yervoy before surgery led to a 27% reduction in the risk of disease recurrence within the first 12 months. Specifically, there were 28 disease-related events in the group receiving the combination therapy before surgery, compared to 72 events in the group receiving adjuvant Opdivo post-surgery.

One significant advantage of this neoadjuvant therapy approach is the reduced need for additional adjuvant therapy. Estimates indicated that 83.7% of patients receiving neoadjuvant therapy remained event-free at 12 months, in contrast to 57.2% of those who received only adjuvant therapy. This benefit was consistent across various subgroups, including those with a BRAF mutation. Furthermore, approximately 60% of patients in the Opdivo plus Yervoy arm did not need additional adjuvant therapy due to achieving a major pathologic response and therefore underwent only six weeks of treatment.

However, the neoadjuvant therapy was associated with a higher incidence of serious side effects, reported in 29.7% of patients, compared to 14.7% in the adjuvant therapy group. Despite this, the lead author, Christian Blank, emphasized that the major toxicity or quality of life impairments stemmed more from the surgery itself rather than the immunotherapy.

Blank proposed that the NADINA trial's approach should serve as a model for other neoadjuvant immunotherapy trials, including a response-driven adjuvant therapy component. He suggested that this strategy could significantly reduce hospital time for about 60% of melanoma patients, thereby conserving considerable healthcare resources.