FDA expands nivolumab approval to treat adolescents with Stage IIB/C melanoma

The FDA has approved nivolumab (Opdivo; Bristol Myers Squibb Company) for the adjuvant treatment of patients 12 years and older with completely resected Stage IIB/C melanoma, the company announced on Friday, October 13, 2023.^1,2

The approval, which expands on the adjuvant indication for nivolumab, was based on the phase 3 CheckMate-76K trial (NCT 04099251), a randomized (2:1), double-blind trial featuring 790 patients with Stage IIB/C melanoma. Randomized to nivolumab 480 mg (n = 526) or placebo (n = 264) by intravenous infusion, patients were treated every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity.^1,2

Recurrence-free survival (RFS), defined as the investigator-assessed time between randomization and first recurrence, new primary melanoma, or death (for any cause), was the major efficacy outcome.¹

Median RFS was not reached in the nivolumab group (95% CI: 28.5, not reached) or in the placebo group (95% CI: 21.6, not reached). Hazard ratio (HR) = 0.42 (95% CI: 0.30-0.59 [P < .0001]). At 1 year, RFS rate was 89% (95% CI: 86-92) compared to 79% for placebo (95% CI: 74-84). Fatigue, musculoskeletal pain, rash, diarrhea, and pruritis were the most common adverse reactions, reported in ≥20% of patients.¹

In a pre-specified exploratory subgroup analysis, the unstratified HR was 0.34 (95% CI: 0.20-0.56) for individuals with stage IIB melanoma and 0.51 (95% CI: 0.32-0.81) in Stage IIC melanoma patients. At 1 year, RFS rates by stage for those who received nivolumab were 93% in Stage IIB (95% CI: 89-95) compared to 84% with placebo (95% CI: 77-89). For individuals with Stage IIC, those treated with nivolumab saw an 84% RFS rate (95% CI: 78-88) compared to 72% with placebo (95% CI: 62-80).²

Complete resection of primary melanoma with negative margins and a negative sentinel lymph node within 12 weeks prior to randomization, and Eastern Cooperative Oncology Group (ECOG)³ performance status of 0 or 1 was required for enrollment. Patients with ocular/uveal or mucosal melanoma, any condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications, autoimmune disease, or those with previous melanoma therapy (except surgery) were excluded from the trial.¹

“Following surgical removal of melanoma, patients may believe they are free of disease,” said John M. Kirkwood, MD, distinguished professor of medicine, University of Pittsburgh School of Medicine, co-director, Melanoma Center at UPMC Hillman Cancer Center in a press release. “However, within [5] years of diagnosis, one-third of patients with surgically resected stage IIB and nearly one-half of patients with surgically resected IIC melanoma see their cancer return, underscoring the need for additional treatment options that may help reduce the risk of cancer coming back. The significant recurrence-free survival improvement observed with nivolumab in CheckMate -76K is an important step forward for these patients.”²

Previously, the FDA approved nivolumab for the adjuvant treatment of pediatric and adult patients (12 years and older) with melanoma with involvement of lymph nodes or metastatic disease, who have undergone complete resection. This approval was based on data from the CheckMate-238 trial.²

According to Bristol Myers Squibb, nivolumab is associated with the following warning and precautions, “severe and fatal immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, nephritis with renal dysfunction, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when [nivolumab] is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.”²

Click here for more safety information.²

References:

1. FDA approves nivolumab for adjuvant treatment of Stage IIB/C melanoma. FDA. Press release. October 16, 2023. Accessed October 16, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-adjuvant-treatment-stage-iibc-melanoma?utm_medium=email&utm_source=govdelivery
2. US Food and Drug Administration approves Opdivo (nivolumab) as adjuvant treatment for eligible patients with completely resected Stage IIB or Stage IIC melanoma. Bristol Myers Squibb. Press release. October 13, 2023. Accessed October 16, 2023. 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
3. Azam F, Latif MF, Farooq A, et al. Performance status assessment by using ECOG (Eastern Cooperative Oncology Group) score for cancer patients by oncology healthcare professionals. 2019 Sep 25;12(3):728-736. doi: 10.1159/000503095. PMID: 31616281; PMCID: PMC6792426.