In 2018, the cancer drug larotrectinib quietly became a milestone along the evolving path to approaching cancer therapy: it was the first agent approved to treat a genetic variant, not a specific type of cancer or disease site. And as oncology treatment science progresses, many predict that it won’t be the last—it’s already been joined by pembrolizumab and entrectinib as tumor-agnostic therapies. The key to curing cancer may be hidden in the disease’s genetic code rather than its location in the body.
The changing approach will affect oncology nurses across all disease site subspecialties, but learning more about larotrectinib can help nurses prepare. In their article in the April 2021 issue of the Clinical Journal of Oncology Nursing, Mota-George and Schneider gave an overview of larotrectinib and its implications for oncology nursing practice.
Larotrectinib for Solid Tumors
Nearly 100% of patients with certain rare solid tumors have an NTRK gene fusion, Mota-George and Schneider reported, which promotes cancer development in tumors that have extra or overactive TRK proteins. In more common cancers, the variant is still quite rare, present in only about 1% of adult and pediatric cancers but spanning diagnoses from thyroid to colorectal and lung cancers as well as gliomas, sarcomas, melanomas, and leukemias.
Larotrectinib binds to TRK proteins to block the signaling that promotes cancer growth and may be a treatment option for adult and pediatric patients who meet certain criteria:
- Tumors with NTRK gene fusion and no documented resistance to the variant
- Metastatic disease where surgical resection would result in significant morbidity
- No adequate alternative treatment options or documented progression after previous treatment
In the drug’s clinical trials, researchers reported a 75% overall response rate, 62% partial response, 13% complete response, 13% stable, 9% progression, and 4% unable to be evaluated across various cancers, TRK fusions, and ages. A total of 71% of patients maintained those responses for at least a year, Mota-George and Schneider reported.
Genetic testing is required to determine NTRK gene fusion, and because it can occur in nearly any type of cancer, some have advocated for its inclusion as a standard component during cancer diagnosis, Mota-George and Schneider said. Clinicians may choose to consider it for younger patients, diagnoses associated with a high incidence of NTRK gene fusions, those with no other common genetic alterations, or patients with advanced disease.
The medication is available as an oral capsule or oral solution that patients should take twice each day, with or without food, until they experience disease progression or unacceptable toxicity. Dosing is based on body surface area (BSA): 100 mg twice per day for BSA of 1 m2 or higher and 100 mg/m2 twice per day for BSA less than 1 m2. Adjust the dosage if patients are receiving concurrent CYP3A4 inhibitors (decrease larotrectinib by half) or inducers (double larotrectinib).
Oncology nurses should be aware of larotrectinib’s common adverse events and assess for them at each patient visit. Early recognition and intervention are imperative, because once they progress to grade 3 and 4, larotrectinib must be held until symptoms resolve, return to baseline, or improve to grade 1. The therapy is discontinued completely if symptoms persist longer than four weeks.
The drug’s package insert warns about the risk for neurotoxicity, hepatotoxicity, and fetal toxicity. In larotrectinib’s clinical trials, neurotoxic adverse events occurred in about 53% of patients, with 6% at grade 3. Most (65%) manifested within 90 days of treatment initiation, and reports included delirium, dizziness, gait changes, speech changes, sensation changes, memory deficits, and tremor. Mota-George and Schneider advised nurses to ask patients about gait changes, coordination issues, paresthesia, speech changes, dizziness, neuropathy, decreased appetite, nausea, vomiting, and abdominal pain.
About 45% of patients had elevated liver enzymes, with 6% at grade 3. The adverse event was most prevalent in the first three months, but reports occurred from 1 month–2.5 years. Anemia, decreased absolute neutrophil count (ANC), and elevated AST and ALT were also reported in the clinical trials. Nurses must routinely review laboratory values, assess for symptomatic or asymptomatic anemia, and watch for signs of infection in patients with low ANC, Mota-George and Schneider said.
To support patient adherence to the oral therapy, ensure patients fill and refill their prescriptions on schedule and assess for any financial toxicities that may affect their ability to pay for the treatment. The manufacturer offers a patient assistance program by calling 844-634-TRAK (8725). During each patient visit, reinforce instructions for taking the medication, resolving missed doses, and reporting side effects, and confirm their current medication list, including certain foods and supplements, to prevent drug-drug or drug-food interactions.
Safe handling: Teach patients how to correctly store, prepare, and administer larotrectinib. Because of the warning for fetal toxicity, evaluate and reinforce the need for reliable contraception. The studies did not evaluate whether the agent is transferred through breast milk, so breastfeeding is not recommended while on treatment or for one week after discontinuation.
Side-effect management: Teach patients about symptoms to monitor for and how to report them, including confusion, speech changes, imbalance, and abdominal pain in the right upper quadrant. Patients should not drive or operate heavy machinery if they start noticing neurologic changes. Ensure they report any new medications or supplements so the cancer care team can assess for possible interactions with larotrectinib.
For more information about oncology nursing care for patients receiving larotrectinib therapy, including a case study example, refer to the full article by Mota-George and Schneider.