Significant RFS Benefit Shown With Adjuvant Nivolumab in Stage IIB or IIC Melanoma

Georgina Long, AO, MD, PhD

Adjuvant nivolumab (Opdivo) demonstrated statistically significant and clinically meaningful improvement in recurrence-free survival (RFS) compared with placebo in patients with completely resected stage IIB or IIC melanoma, meeting the primary end point of the phase 3 CheckMate-76K clinical trial (NCT04099251).¹

“Within 5 years after surgery, one third of stage IIB and one half of IIC patients see their cancer return. Helping reduce that risk remains a need to be addressed when it comes to treating melanoma,” said Georgina Long, AO, MD, PhD, co-medical director of Melanoma Institute Australia (MIA) and chair of melanoma medical oncology and translational research at MIA, The University of Sydney, and Royal North Shore and Mater Hospitals, in a press release. “The data from CheckMate76K show that treating with nivolumab in the adjuvant setting for stage IIB and IIC [patients with] melanoma has yielded significant recurrence-free survival benefits and could be an important treatment option for this patient population.”

Results announced by Bristol Myers Squibb showed that adjuvant nivolumab achieved a 58% reduction in the risk of recurrence or death compared with placebo (HR, 0.42; 95% CI, 0.30-0.59; P <.0001). At the 12-month timepoint, the RFS rates were 89% (95% CI, 86%-92%) in the nivolumab arm vs 79% (95% CI, 74%-84%) in the placebo arm.

RFS benefit was carried across the predefined subgroups in the study, including T category and disease stage. Among patients with stage IIB melanoma, the 12-month RFS rate was 93% in the nivolumab arm vs 84% in the placebo arm. In patients with stage IIC melanoma, nivolumab achieved a 12-month RFS rate of 84% compared with 72% in the placebo arm.

“These data add to our growing body of evidence supporting the clinical benefit of [nivolumab] for the treatment of melanoma, from the metastatic setting to earlier stages of cancer,” said Gina Fusaro, PhD, development program lead, melanoma, Bristol Myers Squibb, in the press release. “We are continually seeking to advance our science to develop medicines that can help improve outcomes for people living with cancer.”

In the study, the safety profile of nivolumab appeared to be consistent with the safety profile observed in previous studies. Ten percent of patients experienced grade 3 and 4 treatment-related adverse events (TRAEs) in the nivolumab arm compared with 2% in the placebo arm. Treatment discontinuation due to TRAEs occurred in 15% of the nivolumab arm vs 3% of the placebo arm.

Full results from the prespecified interim analysis of CheckMate-76K will be presented at the 2022 Society for Melanoma Research (SMR) Annual Meeting, which will be held October 17-20, 2022.

CheckMate-76K is an ongoing phase 3, randomized, double-blind study of adjuvant immunotherapy with nivolumab vs placebo after complete resection of stage IIB and stage IIC melanoma. A total of 790 patients with completely resected stage IIB or IIC melanoma were enrolled in the study to be treated with either nivolumab 480 mg for up to 12 months or placebo. In addition to RFS, the study is also evaluating the secondary end point of overall survival, distant metastases-free survival, progression-free survival on next-line therapy, and safety.²

Patients enrolled had a negative sentinel lymph node biopsy, were previously treated for melanoma, ECOG performance status of 0 or 1, and histologically confirmed disease. The study excluded patients who had a history of ocular or mucosal melanoma, active known or suspected autoimmune disease, known history of allergy or hypersensitivity to the study drug. Moreover, patients who were pregnant or nursing, and patients who were previously treated with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody, or agents that target IL-2 pathways, T-cell stimulators, or checkpoint pathways were ineligible to enroll in the study.

_REFERENCES:

_{1. Bristol Myers Squibb presents data from CheckMate76K showing Opdivo (nivolumab) reduced the risk of recurrence or death by 58% versus placebo in patients with completely resected Stage IIB or IIC melanoma. News release. Bristol Myers Squibb. October 19, 2022. Accessed October 21, 2022. https://bit.ly/3MSOjIt}

_{2. Effectiveness study of nivolumab compared to placebo in prevention of recurrent melanoma after complete resection of stage IIB/C melanoma (CheckMate76K). ClinicalTrials.gov. Updated September 2, 2022. Accessed October 21, 2022. https://clinicaltrials.gov/ct2/show/NCT04099251?term=CheckMate-76K&draw=2&rank=1}