The Third Tissue-Agnostic Cancer Drug Received FDA Approval – Enterectinib

On 15 August 2019, the US Food and Drug Administration (FDA), for adult and adolescent patients whose cancers carry a specific genetic abnormality (NTRK, neurotrophic tyrosine receptor kinase gene fusion) and who have no other effective treatment, granted enterectinib (Rozlytrek) accelerated approval. Enterectinib was also approved for ROS1-positive lung cancers.

The Number of "Tissue-Agnostic" Cancer Treatments (Independent of the Organ Where the Cancer Originated) Is Increasing

Thanks to our growing knowledge of cancer biology, we are in an exciting era of innovation in oncological treatments. For more targeted treatments and more precision oncology , we see biomarker-focused drugs being developed. One of these new cancer biomarkers is NTRK gene fusion.

Enterektinib Is the 3rd Tissue-Agnostic and Biomarker-Based Cancer Treatment Approved by the FDA:

• In 2017, pembrolizumab (Keytruda) received approval for microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors, and
• in 2018, larotrectinib (Vitrakvi) received FDA approval for tumors with NTRK gene fusion (see).

The Studies That Brought FDA Approval to Rozlytrek

• Rozlytrek's ability to shrink tumors was evaluated in four clinical studies involving 54 adults with NTRK fusion-positive tumors.
• The proportion of patients with significant tumor shrinkage (overall response rate) was % 57, and in % 7.4 of patients the tumors disappeared completely (complete response).
• Among 31 patients with tumor shrinkage, in % 61 the treatment response lasted nine months or longer.
• In the studies, common cancer sites with NTRK gene fusion were the lung, salivary gland, breast, thyroid and colon-rectum.

Rozlytrek Was Also Approved for Treating Adults Whose Tumors Are ROS1-Positive (Mutation of the ROS1 Gene) and Have, to Other Parts of the Body, Metastasis Occurred, in Non-Small Cell Lung Cancer.

Clinical studies evaluated ROS1-positive lung cancer in 51 adult patients. The overall response rate was % 78; in % 5.9 of patients, the tumors disappeared completely (complete response). Among 40 patients with significant tumor shrinkage, in % 55 the shrinkage continued for 12 months or longer.

Adverse Effects

Rozlytrek's common adverse effectswere fatigue, constipation, abnormal sense of taste, edema (swelling), dizziness, diarrhea, nausea, dysesthesia (abnormal sensation of touch), shortness of breath, myalgia (muscle pain), cognitive impairment (memory or attention problems, difficulty speaking or hallucinations), weight gain, cough, vomiting, fever, joint pain and visual disturbances (blurred vision, sensitivity to light, double vision, worsening vision, cataracts or floaters).

Rozlytrek's most serious adverse effects include congestive heart failure (weakening of or damage to the heart muscle), central nervous system effects (including cognitive impairment, anxiety, depression including suicidal thoughts, dizziness or loss of balance, changes in sleep patterns including insomnia, and excessive sleepiness), bone fractures, hepatotoxicity (liver damage), hyperuricemia (high uric acid), QT prolongation (abnormal heart rhythm) and visual disturbances.

The FDA granted Rozlytrek accelerated approval (accelerated approval) . Because of this approval, the developer, Genentech, commits to providing additional data to the FDA. Rozlytrek has also received Priority Review, Breakthrough Therapy and Orphan Drug designations.

Image Description: NTRK fusions were first discovered in colon cancer in 1982, but in recent years, new DNA sequencing techniques (next-generation sequencing) and the development of technologies like these have made it possible to detect this abnormality in cancer patients. Scientists have now identified more than 50 different genes that fuse with TRK genes. If TRK genes undergo fusion (joining) as a result of mutation, the resulting abnormal proteins remain constantly "on", sending signals to cancer cells to grow and multiply.