Two targeted therapies get European recommendation for melanoma28 Jul 2015
Novartis has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion for the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.
The Company also announced that the US Food and Drug Administration (FDA) has granted priority review for the same patient population.
The European Committee’s positive opinion is based on results from the Phase 3 COMBI-d and COMBI-v studies.
Combining dabrafenib and trametinib VS dabrafenib monotherapy
The COMBI-d study showed that the combination of dabrafenib and trametinib achieved a statistically significant overall survival benefit compared to dabrafenib monotherapy (median of 25.1 months vs 18.7 months).
- In those who received dabrafenib in combination with trametinib, overall survival was 74% at 1 year and 51% at 2 years versus
- 68% and 42% for those who received dabrafenib only, respectively.
Combining dabrafenib and trametinib VS vemurafenib monotherapy
The COMBI-v study showed that the combination of dabrafenib and trametinib achieved a statistically significant overall survival benefit compared to vemurafenib monotherapy (median for the combination not reached vs 17.2 months).
In the COMBI-v study:
- The rate of overall survival at 1 year was 72% with the combination of dabrafenib and trametinib and
- 65% for those receiving vemurafenib only.
Consistent safety results and manageable adverse events
The safety results from these studies were consistent with the profile observed to date for the combination; no new safety concerns were observed. The most common adverse reactions seen for combination therapy in both studies at >=20% include pyrexia, fatigue, nausea, headache, chills, diarrhea, rash, arthralgia, vomiting, hypertension, and cough.
Adverse events or toxicities were generally manageable with appropriate intervention, as described in the product labeling submitted with the application.
The European Commission will review the CHMP recommendation and is expected to deliver its final decision within three months. The decision will be applicable to all 28 EU member states plus Iceland, Norway and Liechtenstein.
The combination is already approved in the U.S.
Since January 2014, the combination of dabrafenib and trametinib has been approved for use in the US in patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma as detected by an FDA-approved test.
The combination was approved through the FDA's Accelerated Approval program and reviewed under a Priority Review designation. The approval was contingent on the results of the COMBI-d study.
The study was designed to evaluate the clinical benefit of the combination in patients with unresectable or metastatic melanoma with a BRAF V600 mutation. Gene tests can determine whether a tumor has a BRAF mutation, and results can play a key role in prognosis and determining appropriate treatment.
The combination is beneficial also for patients of non-small cell lung cancer with the same mutation
The FDA Breakthrough Therapy designation in BRAF V600 mutation-positive non-small cell lung cancer (NSCLC) is based on interim analysis results from an ongoing single-arm, two-stage, Phase 2 trial investigating the dabrafenib and trametinib combination in patients with metastatic NSCLC who had the BRAF V600E mutation and failed at least one line of chemotherapy.
The most common adverse events (incidence >=20%) among patients included in this analysis were pyrexia, diarrhea, nausea, vomiting, decreased appetite, asthenia, cough, peripheral edema, and rash.Source: eCancer News