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Nivolumab Approved for Adjuvant Treatment of Stage IIB/C Melanoma

Malignant melanoma smear preparation.

The FDA has approved nivolumab (Opdivo®, Bristol Myers Squibb Company) for adjuvant treatment of patients 12 and older with completely resected stage IIB/C melanoma.  

Why it matters: "Patients with resected stage IIB/C melanoma are at high risk of recurrence with outcomes similar to patients with resected stage IIIB disease," wrote Dr. Georgina Long, the Co-Medical Director of Melanoma Institute Australia, and colleagues, in their abstract on the CHECKMATE-76K trial (NCT04099251), on which approval was based. "Adjuvant nivolumab has shown benefit in patients with resected stage III-IV melanoma."

What they studied: Safety and efficacy were studied in the phase 3, double-blind CHECKMATE-76K trial in which 790 patients with completely resected stage IIB/C melanoma were stratified by American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th Edition tumor category and randomized 2:1, to receive either 480 mg of nivolumab (526 patients) or placebo (264 patients) via intravenous infusion every four weeks, for up to one year or until unacceptable toxicity or disease recurrence.

Key eligibility criteria included a complete resection of the primary melanoma with negative margins, a negative sentinel lymph node within 12 weeks prior to randomization, and Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Patients excluded from this trial were those with ocular or mucosal melanoma, an autoimmune disease, any condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications, and those with prior melanoma therapy, not including surgery.

The primary end point measured was recurrence-free survival, which was defined as the investigator-assessed time between randomization and first recurrence, new primary melanoma, or death, whichever occurred first. The key secondary end point measured was distant metastasis–free survival.

What they found: An assessment was conducted every 26 weeks in years one through three and every 52 weeks for the following five years. Nivolumab demonstrated a 58% reduction in the risk of recurrence or death, which was considered statistically significant and clinically meaningful. The median recurrence-free survival was not reached in either the nivolumab arm or the placebo arm. Additionally, a clinically significant improvement in distant metastasis–free survival was observed, with 8% in the nivolumab arm versus 16% in the placebo arm experiencing distant recurrence or death.

What's next: Planned secondary end points to be studied in the future are overall survival and progression-free survival through next-line therapy (PFS2).

Adverse events: The most common adverse events in ≥20% of patients were fatigue, musculoskeletal pain, rash, diarrhea, and pruritis.

Conclusion: "Adjuvant nivolumab significantly improved recurrence-free survival in patients with resected stage IIB/C melanoma by 58% compared with placebo, with clinical benefit observed across disease subgroups, including all tumor (T) categories," concluded John Kirkwood, the Director of the Melanoma Center at the University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, and colleagues, in their publication of the primary results of the CHEKMATE-76K trial. "Nivolumab is an effective adjuvant treatment in resected stage IIB/C melanoma."

Instructions: The recommended dosage of nivolumab for patients weighing ≥40 kg is 240 mg every two weeks or 480 mg every four weeks until disease progression or unacceptable toxicity, for up to one year. The recommended dosage for pediatric patients weighing <40 kg is 3 mg/kg every two weeks or 6 mg/kg every four weeks until disease progression or unacceptable toxicity, for up to one year.

For More Information

Kirkwood J, Del Vecchio M, Weber J, et al (2023). Adjuvant nivolumab in resected stage IIB/C melanoma: primary results from the randomized, phase 3 CheckMate 76K trial. Nat Med. [Epub ahead of print] DOI:10.1038/s41591-023-02583-2

Long GV, Del Vecchio M, Weber J, et al (2023). Adjuvant therapy with nivolumab versus placebo in patients with resected stage IIB/C melanoma (CheckMate 76K). SKIN The Journal of Cutaneous Medicine; 7(2):s163. DOI:10.25251/skin.7.supp.163

Clinicaltrials.gov (2023). Effectiveness study of nivolumab compared to placebo in prevention of recurrent melanoma after complete resection of stage IIB/C melanoma (CheckMate76K). NLM identifier: NCT04099251.

Opdivo® (nivolumab) prescribing information (2023). Bristol Myers Squibb Company. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125554Orig1s121lbl.pdf

US Food and Drug Administration (2023). FDA approves nivolumab for adjuvant treatment of stage IIB/C melanoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-adjuvant-treatment-stage-iibc-melanoma

Bristol Myers Squibb (2023). US Food and Drug Administration approves Opdivo® (nivolumab) as adjuvant treatment for eligible patients with completely resected stage IIB or stage IIC melanoma [news release]. Available at: https://news.bms.com/news/corporate-financial/2023/U.S.-Food-and-Drug-Administration-Approves-Opdivonivolumab-as-Adjuvant-Treatment-for-Eligible-Patients-with-Completely-Resected-Stage-IIB-or-Stage-IIC-Melanoma1/default.aspx

Image credit: Jensflorian. Licensed under CC BY-SA 4.0 DEED


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