FDA Approves Adjuvant Nivolumab in Completely Resected Stage IIB/C Melanoma
Nivolumab is now available as an adjuvant treatment for patients with completely resected stage IIB or IIC melanoma following its approval by the FDA based on data from the phase 3 CheckMate-76k trial.
The News
The FDA has granted approval to nivolumab (Opdivo) as an adjuvant treatment for patients with completely resected stage IIB or IIC melanoma, according to a press release from Bristol Myers Squibb.1
Expert Perspective
“The approval of nivolumab in stage IIB/C melanoma is an important addition to the field. Pembrolizumab [Keytruda] was approved for this indication approximately 2 years ago,2 but having a second agent expands the opportunity space in terms of availability for patients,” Jason J. Luke MD, FACP, said in an interview with CancerNetwork® ahead of the approval.
“The dosing schedule [with nivolumab] can be beneficial. Whereas pembrolizumab is given every 3 weeks or 6 weeks, nivolumab is given on a 4-week schedule. That gives flexibility for patients and doctors.”
Luke is the associate director at Clinical Research Hillman Cancer Center and a director of the Immunotherapy and Drug Development Center at the University of Pittsburgh. He also serves as a melanoma editorial board member for ONCOLOGY®.
Findings from the phase 3 CheckMate-76k trial (NCT04099251) supported the approval of adjuvant nivolumab in this indication.
Supporting Data From CheckMate-76K
Findings from the phase 3 CheckMate-76k trial (NCT04099251) supported the approval of adjuvant nivolumab in this indication.
According to data presented at the 2022 Society for Melanoma Research (SMR) Annual Meeting, treatment with nivolumab produced a 58% reduction in the risk of disease recurrence or death vs placebo with respect to recurrence-free survival (RFS; HR, 0.42; 95% CI, 0.30-0.59; P <.0001).3 Additionally, the 12-month RFS rates in patients receiving nivolumab and placebo, respectively, were 89% (95% CI, 86%-92%) vs 79% (95% CI, 74%-84%).
Investigators reported that RFS benefits with nivolumab extended across predefined subgroups in the trial, including those based on T category and disease stage. The 12-month RFS rates for patients with stage IIB disease were 93% with nivolumab vs 84% with placebo. The corresponding rates for patients with stage IIC disease were 84% vs 72% in each respective treatment arm.
Pharma Perspective
“Following surgical removal of melanoma, patients may believe they are free of disease,” John M. Kirkwood, MD, distinguished professor of medicine at the University of Pittsburgh School of Medicine and co-director of the Melanoma Center at UPMC Hillman Cancer Center, saod in the 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.”
Safety
The safety profile of nivolumab in the CheckMate-76k trial was comparable with previous reports of the agent at the time investigators reported data at the SMR Annual Meeting. Grade 3/4 treatment-related adverse effects (TRAEs) affected 10% of patients receiving nivolumab and 2% of patients receiving placebo.3 Additionally, 15% and 3% of patients in each respective arm discontinued treatment due to TRAEs.
CheckMate-76k Trial Design
Patients with completely resected stage IIB/C melanoma were randomly assigned to receive 480 mg of adjuvant melanoma every 4 weeks for up to 12 months or matched placebo in the double-blind randomized phase 3 CheckMate-76k trial.
The trial’s primary end point was RFS. Secondary end points included distant metastasis-free survival, progression-free survival through next-line therapy, overall survival, and AEs.
Patients 12 years and older with a negative sentinel lymph node biopsy and no prior treatment for melanoma were able to enroll on the trial. Having an ECOG performance status of 0 or 1 was another requirement for enrollment.
The FDA accepted a supplemental biologics license application for adjuvant nivolumab in resected stage IIB or IIC melanoma in February 2023.4
References
- U.S. Food and Drug Administration approves Opdivo® (nivolumab) as adjuvant treatment for eligible patients with completely resected stage IIB or stage IIC melanoma. News release. Bristol Myers Squibb. October 13, 2023. Accessed October 16, 2023. https://bit.ly/3rS28km
- FDA approves pembrolizumab for adjuvant treatment of stage IIB or IIC melanoma. News release. FDA. December 3, 2021. Accessed October 12, 2023. https://shorturl.at/irL23
- Bristol Myers Squibb presents data from CheckMate -76k 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 September 19, 2023. https://bit.ly/3VKfLMH
- U.S Food and Drug Administration accepts Bristol Myers Squibb’s supplemental biologics license application and European Medicines Agency validates application for Opdivo (nivolumab). News release. Bristol Myers Squibb. February 28, 2023. Accessed September 19, 2023. bit.ly/3SEJeXk
