Novartis Announces Long-Term, Relapse-Free Survival Benefit with Tafinlar® + Mekinist® in High-Risk Stage III Melanoma Patients Following Surgery

May 30, 2020 News /BioValleyBIOON/ --Novartis(Novartis) recently announced the milestone COMBI-ADClinical Trialsupdate results, confirming that in patients with high-risk stage III BRAF mutation-positive melanoma, after surgical resectionMelanomaPostoperative adjuvant therapy with the targeted combination of Tafinlar (dabrafenib) and Mekinist (trametinib) provides long-term, durable recurrence-free survival (RFS) benefits.

Researchers reported that 52% (95% CI: 48-58) of patients receiving adjuvant therapy with Tafinlar + Mekinist were alive and recurrence-free at year 5. In the placebo arm of the study, 36% (95% CI: 32-41) of patients were alive and recurrence-free at the time of this analysis, a figure consistent with the typical outcomes observed in untreated patients with resected stage III disease.MelanomaRecurrence-free survival rates were generally consistent. Consistent RFS benefits were observed across all AJCC 7th Edition Stage 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 >1 mm], Stage IIIB, or Stage IIIC) cutaneous melanoma who had undergone complete surgical resection and had not received prior anticancer therapy. In the study, patients were randomly assigned to receive postoperative adjuvant treatment with Tafinlar (150 mg twice daily) plus Mekinist (2 mg once daily) (n=438) or corresponding placebo (n=432) for up to one year. Assessments in the study were conducted according to the 7th edition of the AJCC guidelines.MelanomaStaging; the primary endpoint is recurrence-free survival (RFS), and the secondary endpoints include overall survival (OS), distant metastasis-free survival, recurrence-free analysis, and safety.

The 5-year (60-month) follow-up results announced herein are derived from a prospective analysis of 870 patients with BRAF V600-mutant melanoma who received postoperative treatment with Tafinlar plus Mekinist, representing those with Stage III disease receiving targeted adjuvant therapy.MelanomaThe longest follow-up and largest dataset among patient populations.

At the 5-year data cutoff, the median RFS (i.e., the time at which 50% of patients remained alive and free from recurrence) had not been reached for patients treated with Tafinlar + Mekinist, confirming the long-term benefit of targeted therapy in the adjuvant (postoperative) setting (NR; 95% CI: 47.9 months–NR). The median RFS for patients in the placebo group was 16.6 months (95% CI: 12.7–22.1 months). Compared with placebo, treatment with Tafinlar + Mekinist reduced the risk of recurrence or death by 49% (HR = 0.51; 95% CI: 0.42, 0.61). No updated safety analysis was conducted during the 5-year follow-up, as no patients continued treatment during the extended follow-up period.

Axel Hauschild, MD, Professor of Dermatology at Schleswig-Holstein University Hospital in Germany, stated: “As clinicians, our goal is to provide our stage III patients with the best chance for recurrence-free survival. The results of the COMBI-AD study demonstrate that adjuvant treatment with Tafinlar + Mekinist following surgical resection offers melanoma patients the opportunity for long-term recurrence-free survival. Five years represents a significant clinical and emotional milestone for patients. Recurrent BRAF mutation-positive”MelanomaOnce it spreads to other organs, it can be more dangerous and harder to treat. In the COMBI-AD trial, the durable, long-term outcomes observed in patients clearly demonstrate the important role of targeted therapy in the adjuvant setting.”

NovartisJohn Tsai, M.D., Global Head of Drug Development and Chief Medical Officer, stated, “For patients with melanoma and physicians treating melanoma, the 5-year survival mark is an important predictive milestone. In the COMBI-AD data released today, we found”MelanomaThe risk of recurrence or death was reduced by nearly 50%, and we believe patients will find this information helpful in selecting postoperative treatment options. We thank the participants in this long-termClinical Trialspatients and their families. Their participation and commitment help the community understand how BRAF-targeted therapy benefits resectable stage IIIMelanoma"Patients Reimagine Clinical Treatment Outcomes."

It is estimated that approximately 285,000 new cases of melanoma (stages 0–IV) are diagnosed globally each year, with about half harboring BRAF mutations. Genetic testing can determine the presence of BRAF mutations in tumors. One method for staging melanoma is based on the extent of its metastasis. In stage IIIMelanomain,TumorIt has spread to the regional lymph nodes, with a higher risk of recurrence or metastasis.

Patients with stage III melanoma face a high risk of recurrence after surgical resection of the melanoma, as cancer cells may remain in the body. Generally, most recurrences in patients with stage III melanoma occur within five years. For high-riskMelanomaPostoperative adjuvant therapy can help reduce the risk of disease recurrence.

Tafinlar and Mekinist are both targeted anticancer drugs that respectively target different kinases—BRAF and MEK1/2—within the serine/threonine kinase family of the RAS/RAF/MEK/ERK signaling cascade. Aberrant activation of this signaling pathway is believed to play a role inMelanoma...and plays an important role in the development of other types of cancer. The combination of Tafinlar and Mekinist is more effective at slowing progression than either drug alone.TumorGrowth. Currently,NovartisA global clinical program is underway to evaluate the combination therapy of Tafinlar + Mekinist across a range of typesTumor。

The approved indications for the Tafinlar + Mekinist combination include: (1) treatment of patients with BRAF V600-mutant unresectable or metastatic melanoma, as well as those with resectable Stage III disease; (2) treatment of patients with metastatic non-small cell lung cancer (NSCLC) harboring the BRAF V600E mutation (United States), and treatment of patients with advanced NSCLC harboring BRAF V600 mutations (European Union). Furthermore, Tafinlar and Mekinist have been approved in numerous countries worldwide as monotherapy for the treatment of unresectable or metastatic BRAF V600-mutantMelanomaPatients. (Bioon.com)

Original Source: Novartis announces long-term, relapse-free survival benefit for high-risk, stage III melanoma patients treated with Tafinlar® + Mekinist® following surgery