Novartis recently announced updated results from its landmark COMBI-AD clinical trial, demonstrating that in patients with high-risk stage III BRAF-mutant positive melanoma, adjuvant therapy with the targeted combination therapy Tafinlar (dabrafenib) and Mekinist (trametinib) after surgical resection of melanoma provides a long-term, durable recurrence-free survival (RFS) benefit.
Researchers reported that among patients receiving adjuvant therapy with dabrafenib + trametinib (Tafinlar + Mekinist), 52% (95% CI: 48-58) were relapse-free at year 5. In the placebo group, 36% (95% CI: 32-41) were relapse-free at the time of this analysis, a figure broadly consistent with typical melanoma recurrence-free survival observed in treatment-naïve patients with resected stage III disease. Consistent RFS benefit was observed across all AJCC 7 phase III subgroups.
COMBI-AD was a two-arm, randomized, double-blind, placebo-controlled, pivotal phase III study that enrolled 870 patients with histologically confirmed, BRAF V600E/K mutation-positive, high-risk (stage IIIa [lymph node metastasis >1mm], IIIb, or IIIc) cutaneous melanoma who had undergone complete surgical resection and had not received anticancer therapy. Patients were randomized to receive either Tafinlar (150 mg BID) + Mekinist (2 mg QD) combination therapy (n=438) or the corresponding placebo (n=432) as adjuvant therapy, for a maximum of one year. Melanoma staging was assessed according to AJCC Guideline 7. The primary endpoint was recurrence-free survival (RFS), and secondary endpoints included overall survival (OS), distant metastasis-free survival, recurrence-free profile, and safety.
The 5-year (60-month) follow-up results presented here are from a prospective analysis of 870 patients with BRAF V600-mutant melanoma who received Tafinlar + Mekinist treatment post-surgery. This represents the longest follow-up and largest dataset among patients with stage III melanoma receiving targeted adjuvant therapy.
At the 5-year data cutoff, the median RFS (relapse response time) (i.e., the length of time 50% of patients remained alive and relapse-free) in patients treated with Tafinlar + Mekinist had not yet been reached, confirming the long-term benefit of targeted therapy in adjuvant (post-surgery) treatment (NR; 95% CI: 47.9 months - NR). The median RFS in the placebo group was 16.6 months (95% CI: 12.7–22.1 months). Compared with placebo, Tafinlar + Mekinist treatment reduced the risk of relapse or death by 49% (HR=0.51; 95% CI: 0.42, 0.61). No updated safety analysis was performed during the 5-year follow-up period because no patients continued treatment during the extended follow-up period.
“The 5-year survival rate is a significant predictive milestone for both melanoma patients and physicians treating melanoma,” said Dr. John Tsai, Head of Global Drug Development and Chief Medical Officer at Novartis. “In the COMBI-AD data released today, we found a nearly 50% reduction in the risk of melanoma recurrence or death, and we believe patients will find this information helpful in choosing postoperative treatment options. We thank the patients and their families who participated in this long-term clinical trial. Their participation and commitment help the community understand how BRAF-targeted therapy can reimagine clinical outcomes for patients with resectable stage III melanoma.”
After surgical removal of melanoma, patients with stage III melanoma face a high risk of recurrence because cancer cells may still remain in the body. Typically, most recurrences in stage III melanoma occur within 5 years. Postoperative adjuvant therapy for high-risk melanoma patients can help reduce the risk of recurrence.
