Entrectinib, known as Rozlytrek, is a targeted cancer therapy. It has received U.S. Food and Drug Administration (FDA) approval for specific cancers with particular genetic alterations. This offers a precise approach to treating tumors driven by molecular changes, potentially improving outcomes for eligible patients.
How Entrectinib Works
Entrectinib is a tyrosine kinase inhibitor, blocking proteins that drive cancer growth. It targets tropomyosin receptor kinases (TRK) A, B, and C, which are produced when NTRK genes fuse with other genes. These TRK fusion proteins activate signaling pathways that promote uncontrolled cell proliferation.
The drug also inhibits proto-oncogene tyrosine-protein kinase ROS1 and anaplastic lymphoma kinase (ALK). By inhibiting these specific kinases, entrectinib disrupts abnormal signaling pathways that fuel tumor growth. This suppresses cancer cell proliferation and encourages programmed cell death, leading to tumor shrinkage.
Cancers Entrectinib Treats
Entrectinib is FDA-approved for treating adults with metastatic ROS1-positive non-small cell lung cancer (NSCLC). This lung cancer type accounts for a small percentage of NSCLC cases and is more commonly found in younger, non-smoking individuals.
The medication also has accelerated approval for adults and pediatric patients 12 years and older with solid tumors having a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. This “tumor-agnostic” approval means entrectinib can be used for these gene fusion-positive tumors regardless of their origin. Cancers with NTRK gene fusions can occur in various solid tumor types, including:
Sarcoma
Breast
Thyroid
Colorectal
Cholangiocarcinoma
Gynecological
Neuroendocrine
Non-small cell lung
Salivary gland
Pancreatic
The FDA’s Approval Decision
The FDA granted accelerated approval for entrectinib on August 15, 2019, for both NTRK gene fusion-positive solid tumors and ROS1-positive metastatic NSCLC. This pathway allows earlier access to medications for serious conditions with unmet medical needs, based on tumor response rate and durability. Continued approval may depend on further verification of clinical benefit in ongoing confirmatory trials.
The approval was based on pooled data from three multicenter, single-arm clinical trials: STARTRK-2 (NCT02568267), STARTRK-1 (NCT02097810), and ALKA-372-001. For patients with NTRK fusion-positive solid tumors, an overall response rate of 57% was observed in 54 adult patients, with 68% of responses lasting six months or longer. In 51 adult patients with ROS1-positive metastatic NSCLC, entrectinib demonstrated an overall response rate of 78%, with 55% of responses lasting 12 months or longer.
What Patients Should Know
Entrectinib is administered orally as a 600 mg capsule taken once daily for adults. For pediatric patients aged 12 and older with NTRK gene fusion-positive solid tumors, dosage recommendations are based on body surface area.
Common side effects include:
Fatigue
Constipation
Altered taste (dysgeusia)
Swelling (edema)
Dizziness
Diarrhea
Nausea
Changes in touch sensation (dysesthesia)
Other reported effects include:
Muscle pain
Cognitive impairment
Weight gain
Cough
Vomiting
Fever
Joint pain
Patients should be aware of potential serious side effects, such as:
Congestive heart failure
Central nervous system effects
Skeletal fractures
Liver toxicity
Increased uric acid levels
Vision disorders
Genetic testing is an important step to determine if a patient’s tumor has the specific NTRK gene fusions or ROS1 alterations that make them eligible for entrectinib treatment. For example, the FoundationOne CDx test is approved by the FDA as a companion diagnostic for entrectinib in ROS1 fusion-positive NSCLC or NTRK fusion-positive solid cancers. Healthcare providers will monitor patients for heart function, liver tests, uric acid levels, and vision changes throughout treatment.