Nivolumab vs. Placebo in the Adjuvant Treatment of Patients with Stage IIB/C Melanoma: 3-Year Results of the CheckMate 76K (CM 76K) Study.

Long G, Del Vecchio M, Hoeller C, Weber J, Grob JJ, Morh P, Grabbe S, Dutriaux C, Chiarion-Sileni V, Mackiewicz J, Rutkowski P, Arenberger P, Quéreux G, Meniawy T, Ascierto PA, Taube J, Nassar A, Wang W, Kirkwood JM. Annals of Dermatology and Venereology – FMC, 4, no. 8, Supplement 1, (Dec 01 2024): A94-A95, doi:https://doi.org/10.1016/j.fander.2024.09.527.

Abstract

Introduction

Patients (pts) with resected stage IIB/C melanoma have a high risk of recurrence, similar to that of pts with resected stage IIIB melanoma. The CM 76K trial ( NCT04099251 ) demonstrated a significant reduction in the risk of recurrence or death with nivolumab (NIVO) compared with placebo (PBO) in pts with stage IIB/C melanoma who underwent complete resection. Updated data with 3 years of follow-up are presented here.

Materials and methods

Pts aged  ≥  12 years without evidence of residual disease after resection were stratified according to T category and randomized 2:1 to receive NIVO IV 480  mg or PBO every 4 weeks for 12 months. The primary endpoint was recurrence-free survival (RFS); other endpoints were distant metastasis-free survival (DMFS), safety, and progression-free survival 2 (PFS2). The primary lesion was used to analyze emerging biomarkers.

Results

A total of 790 pts were randomized in a 2:1 ratio to receive NIVO or PBO. With 3 years of follow-up (median of 34.2 months [NIVO] and 33.9 months [PBO]), recurrences occurred in 22% versus 34% of pts, respectively, including distant recurrences in 11% versus 17% of pts; sites of distant recurrence were lung (8% versus 12%), lymph nodes (4% versus 8%), liver (3% versus 3%), and brain (2% versus 4%). NIVO continued to demonstrate improved RFS and DMFS compared with PBO. RFS benefit was also observed in prespecified subgroups, including the T category (HR: 0.59 [95% CI: 0.37–0.94] for T3b, 0.57 [0.31–1.01] for T4a, and 0.65 [0.44–0.96] for T4b). Fewer pts on NIVO received subsequent systemic therapy (12%) compared with PBO (27%), and pts receiving adjuvant NIVO had a sustained benefit compared with PBO beyond the first progression. No new safety signals were observed. At 24 months, the number needed to treat to prevent a recurrence with NIVO was 8 (95% CI: 6–18) and the number needed to induce an additional grade 3–4 adverse event was 8 (95% CI: 6–12).

Discussion

The 3-year follow-up results support the positive benefit-risk profile of adjuvant NIVO as a treatment option for patients with resected stage IIB/C melanoma. The benefit was observed in all subgroups and confirms that NIVO is an effective adjuvant treatment. Biomarker data will be presented.

Conclusion

The 3-year follow-up results show a positive benefit–risk profile of adjuvant NIVO as a treatment option for patients with resected stage IIB/C melanoma. The benefit was observed in all subgroups and confirms that NIVO is an effective adjuvant treatment.