Drugs Xagena
The FDA ( U.S. Food and Drug Administration ) has approved Tabrecta ( Capmatinib ) for the treatment of adult patients with non-small cell lung cancer ( NSCLC ) that has spread to other parts of the body.
Tabrecta is the first FDA-approved therapy to treat NSCLC with specific mutations ( those that lead to mesenchymal-epithelial transition or MET exon 14 skipping ).
The FDA has also approved the FoundationOne CDx assay ( F1CDx ) as a companion diagnostic for Tabrecta.
Most patients had tumor samples that were tested for mutations that lead to MET exon 14 skipping using local tests and confirmed with the F1CDx, which is a next-generation sequencing based in vitro diagnostic device that is capable of detecting several mutations, including mutations that lead to MET exon 14 skipping.
NSCLC is a disease in which malignant cancer cells form in the tissues of the lung. It is the most common type of lung cancer with up to 90% of all lung carcinomas falling into the non-small cell category.
NSCLC occurs when healthy cells become abnormal and grow rapidly. One danger of this form of cancer is that there’s a high likelihood that the cancer cells will spread from the lungs to other organs and body parts.
Cancer metastasis consists of a sequential series of events, and MET exon 14 skipping is recognized as a critical event for metastasis of carcinomas.
Mutations leading to MET exon 14 skipping are found in 3-4% of patients with lung cancer.
Tabrecta is a kinase inhibitor, meaning it functions by blocking a key enzyme that results in helping to stop the tumor cells from growing.
The FDA approved Tabrecta based on the results of a clinical trial involving patients with NSCLC with mutations that lead to MET exon 14 skipping, epidermal growth factor receptor ( EGFR ) wild-type and anaplastic lymphoma kinase ( ALK ) negative status, and at least one measurable lesion.
During the clinical trial, participants received Tabrecta 400 mg orally twice daily until disease progression or unacceptable toxicity.
The major efficacy outcome measure was overall response rate ( ORR ), which reflects the percentage of participants that had a certain amount of tumor shrinkage.
An additional efficacy outcome measure was duration of response ( DOR ).
The efficacy population included 28 patients who had never undergone treatment for NSCLC and 69 previously treated patients.
The ORR for the 28 participants was 68%, with 4% having a complete response and 64% having a partial response. The ORR for the 69 participants was 41%, with all having a partial response.
Of the responding participants who had never undergone treatment for NSCLC, 47% had a duration of response lasting 12 months or longer compared to 32.1% of the responding participants who had been previously treated.
Common side effects for patients taking Tabrecta are peripheral edema, nausea, fatigue, vomiting, dyspnea and decreased appetite.
Tabrecta may cause serious side effects including interstitial lung disease or pneumonitis. Tabrecta should be permanently discontinued in patients with these side effects.
Tabrecta may also cause hepatotoxicity, and health care professionals should monitor a patient’s liver function tests prior to starting and when taking Tabrecta. If a patient experiences hepatotoxicity, Tabrecta should be withheld, dose reduced or permanently discontinued.
Based on a clear positive signal for phototoxicity in laboratory studies in cells, patients may be more sensitive to sunlight and should be advised to take precautions to cover their skin and use sunscreen and not to tan while taking Tabrecta.
Tabrecta may cause harm to a developing fetus or newborn baby. Health care professionals should advise pregnant women of this risk and should advise both females of reproductive potential and male patients with female partners of reproductive potential to use effective contraception during treatment with Tabrecta and for one week after the last dose.
Source: FDA, 2020
XagenaMedicine_2020
