Long-term Survival Benefit Demonstrated with Novartis’ Tafinlar® + Mekinist® in BRAF-Mutant Metastatic Melanoma

June 06, 2019 News /Bio ValleyBIOON/ -- Swiss pharmaceutical giantNovartis(Novartis) recently announced the results of the melanoma milestone COMBI-d and COMBI-v clinical studies: Tafinlar (dabrafenib) + Mekinist (trametinib) combination therapy as first-line treatment for unresectable or metastatic BRAF mutation-positiveMelanomaThe patient also demonstrated long-term survival benefits in both overall survival (OS) and progression-free survival (PFS).

It is worth noting that these pooled analysis results from 563 patients in the aforementioned two studies represent the data for Tafinlar + Mekinist treatment of BRAF V600 mutation-positive unresectable or metastaticMelanomaThe largest-scale data collection and longest follow-up conducted in patients.

Pooled analysis showed that among all patients treated with Tafinlar + Mekinist, the 5-year progression-free survival rate was 19% (95% CI: 15–22%) and the 5-year overall survival rate was 34% (95% CI: 30–38%). In contrast, among patients who achieved a complete response to Tafinlar + Mekinist treatment (19%, n=109), the 5-year progression-free survival rate was 49% and the 5-year overall survival rate was 71%. Researchers also observed that the efficacy of subsequent therapy was maintained in patients who experienced disease progression on the study drug and subsequently received immune checkpoint inhibitor treatment.

In terms of safety, adverse events were reported in 548 out of 559 patients (98%), with no new safety signals identified. Adverse events led to permanent discontinuation of study drug treatment in 99 patients (18%); the most common events were pyrexia (4%), decreased ejection fraction (4%), and increased alanine aminotransferase (1%). No patient deaths related to Tafinlar + Mekinist treatment were reported.

Caroline Robert, MD, Director of the Dermatology Department at the Gustave Roussy Institute in Paris, stated: “Our analysis indicates that first-line treatment with Tafinlar + Mekinist enables approximately one-fifth of patients to achieve five-year disease control and approximately one-third of patients to attain a five-year survival rate. Although metastaticMelanomaHistorically, the prognosis for patients was very poor, but today there are many reasons to be encouraged. Our analysis demonstrated a clinically meaningful positive impact on patient survival. These results suggest that targeted therapy with Tafinlar + Mekinist may provide patients with long-term survival and durable benefits.”

NovartisJohn Tsai, M.D., Global Head of Drug Development and Chief Medical Officer, stated, “The results of the 5-year pooled analysis of COMBI-d/v are truly encouraging, as they demonstrate that many patients with BRAF+ treated with Tafinlar + MekinistMelanoma“The patient’s survival has far exceeded the initial prognosis at the time of diagnosis.”

It is estimated that approximately 280,000 cases are diagnosed globally each year.MelanomaNew cases (Stage 0–IV), approximately half of which harbor BRAF mutations.BiomarkersTesting can determineTumorBRAF mutation status.

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 inMelanomaand plays an important role in the development of other types of cancer. Tafinlar and Mekinist used in combination are more effective at slowing down than either drug aloneTumorGrowth. 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 stage III resectable, unresectable, or metastatic melanoma; (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 more than 60 countries worldwide as monotherapy for the treatment of unresectable or metastatic BRAF V600-mutantMelanomaPatient.(Bioon.com)

Original source:Long-term survival benefit shown for metastatic melanoma patients treated with Novartis Tafinlar® + Mekinist®