DABRAFENIB-TRAMETINIB COMBINATION APPROVED FOR BRAF+ NSCLC

For the first time, a targeted drug combination that has been used in melanoma is nearing the market for use in lung cancer.

The combination consists of the targeted therapies dabrafenib (Tafinlar, Novartis) and trametinib (Mekinist, Novartis), which are already used in the treatment of melanoma in patients whose tumors test positive for the BRAF V600 mutation (about 50% of patients).

Now this combination is nearing approval for use in patients with advanced or metastatic non–small cell lung cancer (NSCLC) whose tumors express the BRAF V600 mutation (about 1% to 3% of this patient population).

The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommended approval of the multiple indication at its February meeting.

This indication is not approved anywhere in the world as yet.

The positive CHMP opinion was based on safety and efficacy data from a phase 2 study in 93 patients with BRAF V600-positive NSCLC (36 treatment-naive and 57 previously treated with chemotherapy).

The 57 patients had experienced tumor progression after receiving at least one platinum-based chemotherapy. In this group of patients, the targeted therapy combination (150 mg of dabrafenib twice daily and 2 mg of trametinib once daily) yielded an overall response rate of 63.2%; the median duration of response was 9.0 months.

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

Rolapitant Also Recommended

Also recommended for approval by the CHMP was rolapitant (Varuby , Tesaro) for the prevention of delayed nausea and vomiting associated with highly and moderately emetogenic cancer chemotherapy in adults. The drug has already been approved in the United States.

Rolapitant (90-mg tablets) acts as an antagonist of substance P/neurokinin 1 (NK-1) receptors. Rolapitant blocks substance P from attaching to nerve cells in the area of the brain that controls vomiting, and this helps prevent nausea and vomiting, according to EMA press materials.

Rolapitant reduces emetic episodes and the use of rescue medicines in the delayed phase (after 24 to 120 hours) in patients treated with highly or moderately emetogenic chemotherapy. The most common side effects are headache, constipation, and fatigue.

The CHMP also recommended generic pemetrexed (Hospira UK Limited) for the treatment of unresectable malignant pleural mesothelioma and locally advanced or metastatic NSCLC other than disease with predominantly squamous cell histology. This generic form of pemetrexed is a powder (100 mg, 500 mg, and 1000 mg) for concentrate for solution for infusion.