FDA approved combination of Novartis tafinlar and mekinist reduces recurrence risk by 53%

Source: Novartis on May 2, 2018 announced that the US FDA has approved the combination of tafinlar (dabrafenib) and mekinist (trametinib) as an adjuvant therapy for BRAF V600E / K melanoma patients In October and December 2017, the FDA awarded the qualification of breakthrough therapy identification and priority review to the combination therapy About 200000 new cases of melanoma are diagnosed every year in the world, and about half of them have BRAF mutations Gene testing can determine whether a tumor has a BRAF mutation Patients with melanoma undergoing surgery have a higher risk of recurrence because melanoma cells can remain in the body after surgery For such patients, adjuvant therapy is usually recommended to reduce the risk of melanoma recurrence Tafinlar plus mekinist combination therapy is such an adjuvant therapy Tafinlar and mekinist target different kinases in the serine / threonine kinase family BRAF and MEK1 / 2 in Ras / Raf / MEK / ERK pathway, respectively They are usually found in non-small cell lung cancer (NSCLC) and melanoma When tafinlar is used with mekinist, its effect on slowing down tumor growth has been proved to be better than that of single drug At present, this combination therapy has been approved in the United States, the European Union, Australia, Canada and other countries to treat unresectable or metastatic melanoma patients with BRAF V600 mutation The approval of this combination therapy is based on the results of clinical trial combi-ad Combi-ad is a randomized, double-blind, placebo-controlled, three-phase study that included 870 patients with BRAF V600E / K mutations who had previously been surgically removed for stage III melanoma These patients were stratified according to BRAF mutation type (V600E vs v600k) and stage (IIIA vs IIIB vs IIIc), and randomly assigned to receive tafinlar (150mg bid) plus mekinist (2mg QD) for 12 months or matched placebo (n = 432) The primary end point of the study was relapse free survival (RFs) The secondary end points included total survival (OS), distant metastasis free survival (DMFS), relapse free (FFR) and safety After a median follow-up of 2.8 years, the study reached the primary end point of relapse free survival (RFs) Compared with placebo, combination therapy significantly reduced the risk of disease recurrence or death by 53% (HR: 0.47, 95% CI: 0.39-0.58, P < 0.0001) The median RFs of the combination therapy was not achieved, and the placebo was 16.6 months The efficacy of combination therapy on RFs was observed in all patient subgroups and disease subgroups The combination therapy also improved the key secondary endpoints such as OS, DMFS and FFR Adverse events in combination therapy were consistent with those in other studies and no new safety issues were identified The results were published in the New England Journal of medicine "The purpose of adjuvant therapy is to improve the relapse free and overall survival of patients with melanoma, and adjuvant therapy is critical today because more than half of patients relapse after surgery," said John M "We developed the first FDA approved adjuvant therapy 22 years ago, and now we have the first effective oral targeted combination therapy that can prevent the recurrence of melanoma patients with BRAF mutations that spread to the lymph nodes," Dr Kirkwood said "Prevention and early detection are important safeguards for melanoma, but this is only part of it Melanoma is an aggressive cancer that can recur, especially when it shows some warning signs, such as increased depth, ulcers or spread to lymph nodes, "said sancy, head of dermatology at the University of health and Science in Oregon (OHSU) School of Medicine "After these patients have proven new therapies, dermatologists need to make sure that the right patients can use adjuvant therapies," Dr Leachman said The method of "observation and waiting" is no longer a standard of care Working with a multidisciplinary care team of surgeons, pathologists, and oncologists, it is critical to our patient care plan to determine the right treatment plan based on the patient's personal situation and mutation status " We hope that the approval of this new combination therapy can bring hope for the survival of the majority of patients with melanoma.