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

The combination has already shown utility in treating skin cancers with BRAF mutations, with trametinib and dabrafenib having multiple other indications as solo agents or in other combinations

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 organisations recommend genetic testing for patients with lung cancer.

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 trametinib and dabrafenib 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  dabrafenib twice daily and 2 mg of trametinib 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 >20%) were pyrexia, nausea, vomiting, diarrhoea, asthenia, decreased appetite, dry skin, chills, peripheral oedema, cough and rash.

Updated data from the previously treated and treatment-naïve cohorts were included in the overall data package for EMA review and will also be presented at upcoming medical meetings.

The European Commission (EC) typically adheres to the recommendation of the CHMP and usually delivers its final decision within two months.

The decision will be applicable to all 28 European Union (EU) member states plus Iceland and Norway.

“At Novartis, we are committed to finding treatments for rare cancers with an unmet need. Today’s CHMP opinion marks a major milestone for NSCLC patients with the BRAF V600 mutation, who have very limited treatment options,” said Bruno Strigini, CEO, Novartis Oncology, who market trametinib and dabrafenib as Tafinlar and Mekinist, respectively. “We welcome the CHMP’s opinion as a first step towards that goal, and look forward to continuing to work with European health authorities to make Tafinlar Mekinist available for appropriate NSCLC patients.”

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

Combination use of trametinib and dabrafenib is also approved in the US, Australia, Canada and additional countries for patients with unresectable or metastatic melanoma whose tumours tested positive for the BRAF V600 mutation.

Source: EMA