Martin Dietrich, MD from Florida Cancer Specialists speaks about the FDA Approves FoundationOne®CDx as Companion Diagnostic for Vitrakvi® (larotrectinib), to Aid in Identifying NTRK Fusion-Positive Patients.
WHIPPANY, N.J."(BUSINESS WIRE)"According to Bayer, the U.S. Food and Drug Administration (FDA) approved FoundationOne®CDx for use as the first complementary diagnostic to help classify fusion-positive patients with neurotrophic receptor tyrosine kinase (NTRK) for whom Vitrakvi® (larotrectinib) treatment may be appropriate.1,2 FoundationOne CDx is an FDA-approved extensive genomic profiling (CGP) test for all solid tumors that includes multiple com com tumors.
Vitrakvi is approved for the treatment of adult and pediatric patients with solid tumors who, without an established acquired resistance mutation, have NTRK gene fusion, are metastatic, or are likely to have significant morbidity due to surgical resection and do not have adequate alternative therapies or who have progressed after treatment. Under accelerated approval, this indication is approved based on the average response rate and response period. In confirmatory trials, continued approval of this indication may be dependent upon verification and explanation of the clinical benefit.
Vitrakvi® (larotrectinib) 2 About Vitrakvi 2
Vitrakvi® (larotrectinib) is indicated in the U.S. for the treatment of adult and pediatric patients with solid tumors that have an NTRK gene fusion without a known acquired resistance mutation, are either metastatic or are likely to have serious morbidity due to surgical resection, and do not have adequate alternative therapies or have progressed after therapy.
Under accelerated approval, this indication is approved based on the average response rate and response period. In confirmatory trials, continued approval of this indication may be dependent upon verification and explanation of the clinical benefit.
In 42 countries including the United States, Canada, Brazil, and the European Union, Vitrakvi is approved (EU). Additional filings are ongoing or expected in other areas.
Relevant details on the protection of Vitrakvi® (larotrectinib)
Neurotoxicity: Among the 176 patients who received VITRAKVI, 53% of patients experienced neurologic adverse reactions of any grade, including Grade 3 and Grade 4 neurologic adverse reactions in 6% and 0.6% of patients respectively. In the first three months of therapy, the majority (65%) of neurologic adverse reactions occurred (range 1 day to 2.2 years). Delirium (2%), dysarthria (1%), dizziness (1%), gait disorder (1%), and paresthesia were Grade 3 neurologic adverse reactions (1 percent ). In a single patient, Grade 4 encephalopathy (0.6 percent) occurred. Dizziness (3 percent), gait disturbance (1 percent), delirium (1 percent), memory decline (1 percent), and tremor were neurologic adverse reactions contributing to dose change (1 percent ).
Notify VITRAKVI patients and caregivers of these threats. If you encounter neurological adverse reactions, warn patients not to drive or run dangerous machinery. Withhold or discontinue VITRAKVI indefinitely depending on severity. If it is withheld, alter the dosage of VITRAKVI when it is resumed.
Hepatotoxicity: Increased transaminases of any grade occurred in 45% of the 176 patients who received VITRAKVI, including Grade 3-increased AST or ALT in 6% of patients. A Grade 4 increased ALT was experienced by one patient (0.6 percent). The median time to initiate elevated AST was 2 months (range: 1 month to 2.6 years). The median time to initiate elevated ALT was 2 months (range: 1 month to 1.1 years). Increased AST and ALT resulting in dosage increases occurred in 4% and 6% of patients respectively. In 2 percent of patients, increased AST or ALT contributed to permanent discontinuation.
For the first month of treatment, control liver tests, including ALT and AST, every 2 weeks, then weekly afterward, and as clinically indicated. Withhold or discontinue VITRAKVI indefinitely depending on severity. If withheld, when resumed, change the dose of VITRAKVI.
Embryo-Fetal Toxicity: When given to a pregnant woman, VITRAKVI can cause fetal damage. Larotrectinib resulted in malformations at maternal exposures in rats and rabbits that were approximately 11- and 0.7-fold, respectively, in those reported at the 100 mg twice-daily clinical dose.
Notify women of the possible danger of producing a pregnancy. Advise women with the reproductive capacity to use an appropriate form of contraception before and for 1 week after the final dose of VITRAKVI during treatment.
Most common adverse reactions (about 20%): The most common adverse reactions (about 20%) were: increased ALT (45%), increased AST (45%), anemia (42%), fatigue (37%), nausea , dizziness (28%), cough (26%), vomiting , constipation (23%), and diarrhea (22 percent ).
Drug Interactions: Avoid co-administration of VITRAKVI with potent inhibitors of CYP3A4 (including grapefruit or grapefruit juice), potent inducers of CYP3A4 (including St. John’s wort), or responsive substrates of CYP3A4. If it is not possible to prevent co-administration of powerful CYP3A4 inhibitors or inducers, adjust the dose of VITRAKVI as prescribed. If it is not possible to prevent co-administration of susceptible CYP3A4 substrates, monitor patients for increased adverse reactions to these medicines.
Lactation: Advise women not to breastfeed during and for 1 week after the final dose of VITRAKVI care.
Around TRK Merger Cancer
When an NTRK gene fuses with another unrelated gene, TRK fusion cancer occurs, producing an altered TRK protein. The altered protein becomes constitutively active or overexpressed, inducing a signaling cascade, or TRK fusion protein. The oncogenic drivers of these TRK fusion proteins promote cell growth and survival, leading to TRK fusion cancer, regardless of where it originates in the body. TRK fusion cancer can occur in any part of the body and is not confined to certain types of tissues. TRK fusion cancer occurs with different frequencies of adult and pediatric solid tumors, including lung, thyroid, GI (colon, cholangiocarcinoma, pancreatic and appendiceal), sarcoma, CNS (glioma and glioblastoma), salivary gland (mammary analog secretory carcinoma), and pediatric cancers (infantile fibrosarcoma and soft tissue sarcoma).