Larotrectinib / Vitrakvi (Everest)

Product Overview

Larotrectinib (Brand name: Vitrakvi) manufactured by Everest Pharma is a targeted TRK inhibitor used for the treatment of adult and pediatric patients with locally advanced or metastatic solid tumors harboring NTRK gene fusions, regardless of the tumor’s site of origin.

Larotrectinib became the first FDA-approved tumor-agnostic targeted therapy based solely on a genetic mutation rather than cancer type. Clinical studies demonstrated efficacy across 17 different adult and pediatric tumor types.

🧬 Mechanism of Action

Larotrectinib is an NTRK gene inhibitor targeting the NTRK gene family:

• NTRK1
• NTRK2
• NTRK3

When these genes fuse with other genes, they may become abnormally activated and drive cancer development. NTRK gene fusions have been identified across multiple tumor types, and Larotrectinib is considered a preferred targeted treatment option for these cancers.

📊 Clinical Efficacy

Clinical studies demonstrated strong activity across 17 solid tumor types:

• Objective Response Rate (ORR): 75%
• Complete Response (CR): 22%
• Partial Response (PR): 53%

Pediatric Tumors

Larotrectinib has also been extensively studied in pediatric cancers, with treatment response rates reaching as high as 93% in certain childhood tumor types.

Brain Tumors & CNS Metastases

For patients with NTRK fusion-positive brain tumors:

• Progression-free survival rate: 36%

For metastatic brain tumors:

• Progression-free survival rate: 60%

These encouraging CNS outcomes contributed significantly to the widespread attention Larotrectinib received following its FDA approval in November 2018.

📌 Indications

Larotrectinib capsules are indicated for adult and pediatric patients with solid tumors who meet all of the following criteria:

• Tumors confirmed to harbor an NTRK gene fusion by validated testing methods
• No known acquired resistance mutations present
• Locally advanced or metastatic disease, or tumors where surgical resection would likely cause severe complications
• No satisfactory alternative treatment options or disease progression following prior therapy

💊 Dosage and Administration

Important Testing Requirement

Before treatment begins, patients must undergo validated testing to confirm the presence of an NTRK fusion gene in tumor samples.

Patients identified as fusion-positive by hospitals or laboratories may receive treatment, with additional confirmation recommended through an authorized independent review process.

Adult Dosage

• Recommended dose: 100 mg orally twice daily
• Continue treatment until disease progression or unacceptable toxicity occurs

Pediatric Dosage

Pediatric dosing is based on body surface area (BSA):

• Recommended dose: 100 mg/m² orally twice daily
• Maximum dose: 100 mg per dose

Continue treatment until disease progression or unacceptable toxicity occurs.

⏰ Missed Dose Instructions

• Do not take a double dose to make up for a missed dose
• Resume treatment at the next scheduled dosing time
• If vomiting occurs after taking a dose, do not take an additional dose

⚠️ Dose Modification Guidelines

Grade 2 Adverse Reactions

• Treatment may generally continue with close monitoring
• Patients with Grade 2 ALT and/or AST elevation should undergo laboratory monitoring every 1–2 weeks

Grade 3 or 4 Adverse Reactions

• Interrupt treatment until adverse reactions improve to baseline or Grade 1
• If recovery occurs within 4 weeks, treatment may resume at a reduced dose
• Permanently discontinue treatment if toxicity does not resolve within 4 weeks