ly 11- and 0.7-times, respectively, those observed at the clinical dose of 100 mg twice daily. Advise women ofthe potential risk to a fetus. Advise females of reproductive potential to use an effective methodof contraception during treatment and for 1 week after the final dose of VITRAKVI [see Use inSpecific Populations (8.1, 8.3)].
6 ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in the labeling:
• Neurotoxicity [see Warnings and Precautions (5.1)]
• Hepatotoxicity [see Warnings and Precautions (5.2)]
6.1 Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction ratesobserved in the clinical trials of a drug cannot be directly compared to rates in the clinical trialsof another drug and may not reflect the rates observed in practice.
Data in WARNINGS AND PRECAUTIONS and below reflects exposure to VITRAKVI in176 patients, including 70 (40%) patients exposed for greater than 6 months and 35 (20%) patientsexposed for greater than 1 year. VITRAKVI was studied in one adult dose-finding trial[LOXO-TRK-14001 (n = 70)], one pediatric dose-finding trial [SCOUT (n = 43)], and one singlearm trial [NAVIGATE (n = 63)]. All patients had an unresectable or metastatic solid tumor and nosatisfactory alternative treatment options or disease progression following treatment.
Across these 176 patients, the median age was 51 years (range: 28 days to 82 years); 25% were18 years or younger; 52% were male; and 72% were White, 11% were Hispanic/Latino, 8% wereBlack, and 3% were Asian. The most common tumors in order of decreasing frequency were softtissue sarcoma (16%), salivary gland (11%), lung (10%), thyroid (9%), colon (8%), infantilefibrosarcoma (8%), primary central nervous system (CNS) (7%), or melanoma (5%). NTRK genefusions were present in 60% of VITRAKVI-treated patients. Most adults (80%) receivedVITRAKVI 100 mg orally twice daily and 68% of pediatrics (18 years or younger) receivedVITRAKVI 100 mg/m2 twice daily up to a maximum dose of 100 mg twice daily. The doseranged from 50 mg daily to 200 mg twice daily in adults and 9.6 mg/m2 twice daily to120 mg/m2 twice daily in pediatrics [see Pediatric Use (8.4)].
The most common adverse reactions (≥ 20%) in order of decreasing frequency were fatigue,nausea, dizziness, vomiting, anemia, increased AST, cough, increased ALT, constipation, anddiarrhea.
The most common serious adverse reactions (≥ 2%) were pyrexia, diarrhea, sepsis, abdominalpain, dehydration, cellulitis, and vomiting. Grade 3 or 4 adverse reactions occurred in 51% ofpatients; adverse reactions leading to dose interruption or reduction occurred in 37% of patientsand 13% permanently discontinued VITRAKVI for adverse reactions.
The most common adverse reactions (1-2% each) that resulted in discontinuation of VITRAKVIwere brain edema, intestinal perforation, pericardial effusion, pleural effusion, small intestinalobstruction, dehydration, fatigue, increased ALT, increased AST, enterocutaneous fistula,increased amylase, increased lipase, muscular weakness, abdominal pain, asthenia, decreasedappetite, dyspnea, hyponatremia, jaundice, syncope, vomiting, acute myeloid leukemia, andnausea.
The most common adverse reactions (≥ 3%) resulting in dose modification (interruption orreduction) were increased ALT (6%), increased AST (6%), and dizziness (3%). Most (82%)adverse reactions leading to dose modif |
