The New England Journal of MedicineNeoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma

Efficacy of Neoadjuvant Immunotherapy in Stage III Melanoma: Insights into Event-Free Survival and Pathological Response

In a phase 3 trial, researchers evaluated the efficacy of neoadjuvant versus adjuvant immunotherapy in patients with resectable, macroscopic stage III melanoma. This study aims to determine the potential benefits of neoadjuvant ipilimumab plus nivolumab followed by surgery and response-driven adjuvant therapy compared to the traditional approach of surgery followed by adjuvant nivolumab.

Study Design:

• Participants: 423 patients with resectable, macroscopic stage III melanoma.
• Intervention: Random assignment to neoadjuvant ipilimumab plus nivolumab followed by surgery or surgery followed by 12 cycles of adjuvant nivolumab.
• Primary End Point: Event-free survival.
• Follow-up: Median of 9.9 months.

Key Findings:

• Event-Free Survival: At 12 months, the estimated event-free survival was 83.7% in the neoadjuvant group versus 57.2% in the adjuvant group (hazard ratio for progression, recurrence, or death: 0.32; P<0.001).
• Pathological Response: In the neoadjuvant group, 59.0% had a major pathological response, 8.0% had a partial response, 26.4% had a nonresponse, and 2.4% had progression.
• Recurrence-Free Survival: Among those with a major pathological response in the neoadjuvant group, the 12-month recurrence-free survival was 95.1%, compared to 76.1% for partial responders and 57.0% for nonresponders.
• Adverse Events: Grade 3 or higher adverse events related to systemic treatment occurred in 29.7% of the neoadjuvant group and 14.7% of the adjuvant group.

HCN Medical Memo
Neoadjuvant immunotherapy using ipilimumab plus nivolumab in patients with resectable, macroscopic stage III melanoma demonstrates a promising improvement in event-free and recurrence-free survival rates.

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