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The Committee for Medicinal Products for Human Use ( CHMP ) of the European Medicines Agency ( EMA ) has adopted a positive opinion recommending approval of Tafinlar ( Dabrafenib ) in combination with Mekinist ( Trametinib ) to treat patients with advanced or metastatic non-small cell lung cancer ( NSCLC ) whose tumors express the BRAF V600 mutation.

If approved, Tafinlar in combination with Mekinist will be the first targeted treatment available for patients with BRAF V600-positive NSCLC.
Of the estimated 1.8 million new cases of lung cancer diagnosed worldwide each year, 1-3%, may be driven by the BRAF mutation.

The positive CHMP opinion was based on safety and efficacy data from a phase II study of Tafinlar in combination with Mekinist in patients with BRAF V600-positive NSCLC ( 36 treatment-naïve and 57 previously treated with chemotherapy ).

The 57 patients who had tumor progression on at least one Platinum based chemotherapy, receiving 150 mg of Tafinlar twice daily and 2 mg of Mekinist once daily, demonstrated an overall response rate ( ORR ) of 63.2% ( 95% confidence interval [ CI ], 49.3%, 75.6% ) and duration of response of 9.0 months ( 95% CI, 6.9, 18.3 months ).

The most common adverse events ( incidence more than 20% ) were pyrexia, nausea, vomiting, diarrhea, asthenia, decreased appetite, dry skin, chills, peripheral edema, cough and rash.

The European Commission ( EC ) typically adheres to the recommendation of the CHMP and usually delivers its final decision within two months.
In Europe, Tafinlar and Mekinist is approved for the treatment of patients with unresectable or metastatic melanoma who have a BRAF V600 mutation.

The US Food and Drug Administration ( FDA ) granted Tafinlar + Mekinist Breakthrough Therapy Designation for advanced or metastatic BRAF V600-positive NSCLC patients in 2015 and Priority Review in November 2016.

Worldwide, lung cancer causes more deaths than colon, breast, and prostate cancer combined, and an estimated 1.8 million new cases of lung cancer are diagnosed each year.
Among patients with NSCLC, roughly 30% have an actionable mutation that may be targeted with available therapies. To determine that treatment, medical organizations recommend genetic testing for patients with lung cancer.

Tafinlar and Mekinist target different kinases within the serine/threonine kinase family - BRAF and MEK1/2, respectively - in the RAS/RAF/MEK/ERK pathway, which is implicated in non-small cell lung cancer and melanoma, among other cancers.
When Tafinlar is used with Mekinist, the combination has been shown to slow tumor growth more than either drug alone. ( Xagena )

Source: Novartis, 2017

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