Highly significant event-free survival benefit with neoadjuvant nivolumab/ipilimumab in stage III melanoma

Two courses of neoadjuvant treatment with nivolumab/ipilimumab improved event-free survival (EFS) in patients with macroscopic stage III melanoma, compared with standard adjuvant nivolumab, in the phase 3 NADINA trial.

The standard management of resectable, macroscopic stage III melanoma is currently surgery, which can be followed by adjuvant systemic therapy. Despite adjuvant systemic treatment, a substantial proportion of patients experience recurrence within the first few years after surgery. Additionally, none of the approved adjuvant immunotherapies has shown a significant overall survival (OS) benefit despite long-term follow-up [1,2].

Previously, neoadjuvant treatment with nivolumab/ipilimumab resulted in higher pathological response and EFS compared with neoadjuvant PD-1 blockade [3]. The NADINA trial (NCT04949113) is the first randomised, phase 3 trial to compare neoadjuvant nivolumab/ipilimumab with the current standard-of-care of adjuvant anti-PD-1. Prof. Christian Blank (Antoni van Leeuwenhoek, the Netherlands) presented the results [4].

NADINA randomised 423 participants 1:1 to surgery followed by 12 courses of nivolumab (480 mg every 4 weeks) or to 2 courses of nivolumab (240 mg) plus ipilimumab (80 mg) followed by surgery. Participants who had a major pathological response did not receive any additional treatment; those without a major pathological response received 11 courses of nivolumab (480 mg) or dabrafenib/trametinib (in case of BRAF V600E/K mutation)

The EFS rate at 12 months after randomisation was 83.7% with neoadjuvant treatment and 57.2% with adjuvant treatment (HR 0.32; 99.9% CI 0.15–0.66; P<0.0001; see Figure). The EFS benefit of neoadjuvant treatment was observed in all prespecified subgroups (e.g BRAF wildtype vs BRAF V600E/K).

Figure: Event-free survival in NADINA [4]



Among the neoadjuvant-treated participants, 59% had a major pathological response and did not receive any adjuvant treatment. The 12-month EFS rate in participants who achieved a major pathological response was 95%.

“The neoadjuvant combination of nivolumab/ipilimumab resulted in a highly statistically significant EFS benefit compared with standard-of-care adjuvant PD-1 blockade in patients with macroscopic, resectable stage III melanoma. Nearly 60% of patients in the neoadjuvant therapy arm required only 6 weeks of treatment,” concluded Prof. Blank.

1. Eggermont AMM, et al. NEJM Evidence 2022;1:EVIDoa2200214.
2. Larkin J, et al. Clin Cancer Res 2023;29:3352-3361.
3. Platel SP, et al. N Engl J Med 2023;388:813-823.
4. Blank CU, et al. Neoadjuvant nivolumab plus ipilimumab versus adjuvant nivolumab in macroscopic, resectable stage III melanoma: the phase 3 NADINA trial. Abstract LBA3502, ASCO Annual Meeting 2024, 31 May–4 June, Chicago, IL, USA.

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Posted on 18 July 202419 July 2024