Canafenib in the treatment of BRAF mutated lung cancer xa0

On October 11, 2023, the U.S. Food and Drug Administration approved encorafenib (Braftovi) and binimetinib (Mektovi) for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutations detected by a U.S. FDA-approved test.

Canafenib is a kinase inhibitor that targets BRAF V600E as well as wild-type BRAF and CRAF in in vitro cell-free assays with IC50 values of 0.35, 0.47 and 0.3 nM, respectively. BRAF gene mutations, such as BRAF V600E, can lead to sustained activation of BRAF kinase, thereby stimulating tumor cell growth. Encorafenib also binds to other kinases in vitro, including JNK1, JNK2, JNK3, LIMK1, LIMK2, MEK4, and STK36, and reduces ligand binding to these kinases at clinically achievable concentrations (≤0.9 µM).

The U.S. FDA also approved FoundationOne CDx (tissue) and FoundationOne Liquid CDx (plasma) as companion diagnostics for canafenib and bimetinib. If mutations are not detected in the plasma sample, tumor tissue should be tested.

PHAROS (NCT03915951) was an open-label, multicenter, single-arm study evaluating efficacy in 98 patients with BRAF V600E-mutated metastatic NSCLC. No previous use of BRAF or MEK inhibitors was allowed. Patients received canafenib and bimetinib until disease progression or unacceptable toxicity.

The primary efficacy outcome measures were objective response rate (ORR) and duration of response (DoR) according to RECIST v1.1 As assessed by an independent review committee. Among 59 treatment-naïve patients, the ORR was 75% (95% CI: 62, 85); the median DoR was not estimable (NE) (95% CI: 23.1, NE). Among 39 previously treated patients, the ORR was 46% (95% CI: 30, 63) and the median DoR was 16.7 months (95% CI: 7.4, NE).

The most common adverse reactions of canafenib (≥25%) are fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash, and cough.

The recommended dosage for BRAF V600E mutation-positive NSCLC is canafenib 450 mg orally once daily and bimetinib 45 mg orally twice daily.

As of now, canafenib is not yet available in China, and domestic patients cannot directly obtain this drug. According to reports, the drug has been sold in Europe, with the price of 75 mg and 42 pills being about 17,000 yuan, and the price of 75 mg and 168 pills being close to 59,000 yuan. If the patient needs canafenib, please consult a formal overseas medical consultation service.