Major Research Findings

Larotrectinib is a targeted therapy drug effective in treating tumors positive for NTRK fusion, and many studies have confirmed its efficacy and safety. 16 reported that in a patient with soft tissue sarcoma metastatic to the lung, an LMNA-NTRK1 gene fusion was detected and that treatment with larotrectinib resulted in rapid tumor shrinkage and improvements in dyspnea, oxygen saturation, and plasma tumor markers. 9 reported a case of a newborn with infantile fibrosarcoma where treatment with standard doses of larotrectinib resulted in significant mass shrinkage without any adverse effects, demonstrating the effect of targeted therapy. 6 reported that larotrectinib was well tolerated and showed durable responses in patients with tumors bearing NTRK fusions. 15 reported that larotrectinib is effective for NTRK-positive tumors regardless of the histology or age group, showing efficacy in a wide range of diseases including rare pediatric tumors, salivary gland tumors, gliomas, soft-tissue sarcomas, and thyroid carcinomas. 8 reported that in two patients with infant high-grade gliomas who had NTRK fusion, larotrectinib treatment achieved complete remission and a very good partial response, respectively, without any severe side effects. 17 reported that TRK inhibitors such as larotrectinib have shown efficacy in various patients with TRK fusion-positive cancers, including those with locally advanced or metastatic disease and intracranial activity has been observed with both agents in TRK fusion-positive solid tumors with brain metastases and primary brain tumors. 7 reported a case of an abdominal infantile fibrosarcoma diagnosed in a newborn associated with an aortic aneurysm that was successfully treated with larotrectinib without relevant adverse effects. 4 reported that larotrectinib showed efficacy in patients with TRK fusion-positive thyroid carcinoma. 3 reported that while NTRK gene fusions are not common in most cancers, they are present in more than 90% of some rare tumors. 14 reported a case of a patient with NTRK fusion-positive sarcoma who had tumor progression after 4 months of entrectinib use, but subsequently took larotrectinib and maintained disease control for more than 21 months. 13 reported that CZw-124, a quinazoline derivative, is a pan-TRK inhibitor with potent anticancer effects in vitro and in vivo. 5 reported a case of a newborn with a large NTRK fusion-positive infantile fibrosarcoma who experienced a rapid clinical and radiographic response to larotrectinib treatment. 1 reported a case of a high-grade sarcoma patient with dual STRN-NTRK2 rearrangements who showed good clinical response to first-line larotrectinib therapy. 10 reported that TRK fusions are present in various cancers in adults and children and that despite occurring in fewer than 1% of solid tumors, inhibition of TRK resulted in profound therapeutic responses. 2 reported that larotrectinib showed efficacy and safety in patients with TRK fusion-positive lung cancers. 18 reported a case of a patient with mesoblastic nephroma metastatic to bone who had a dramatic response to larotrectinib. 12 reported that 6,6-dimethyl-4-(phenylamino)-6H-pyrimido[5,4-b][1,4]oxazin-7(8H)-one derivatives are a new class of pan-Trk inhibitors. 19 reported that larotrectinib is a good case study of the development of a tumor-agnostic drug relevant to children. 11 reported a novel in-cell ELISA method for screening compounds inhibiting TRKA phosphorylation, using KM12 cells harboring TRKA rearrangement.

Benefits and Risks

Benefits Summary

Larotrectinib has the potential to reduce tumor size, control disease progression, and improve symptoms in patients with NTRK fusion-positive tumors. 16 , 9 , 8 , 14 Larotrectinib may be effective regardless of tumor histology or age. 15 Larotrectinib may also be effective in patients with brain metastases or primary brain tumors. 17 Larotrectinib may be safe for use in newborns and children. 9 , 5 Larotrectinib may be more effective when combined with other therapies. 8

Risks Summary

The risks associated with using larotrectinib include side effects such as weight gain, dizziness/ataxia, and paresthesias. 17 Larotrectinib may not be effective for all patients and drug resistance may occur. 17 Larotrectinib should not be used by pregnant or breastfeeding women. 17

Comparison Between Studies

Commonalities

Larotrectinib has shown efficacy and safety in treating NTRK fusion-positive tumors. 16 , 9 , 6 , 15 , 8 , 17 , 7 , 4 , 3 , 14 , 13 , 5 , 1 , 10 , 2 , 18 , 12 , 19 , 11 Larotrectinib may be effective regardless of the histology or age of the tumor. 15 , 3 , 19 Larotrectinib may also be effective in patients with brain metastases or primary brain tumors. 17 Larotrectinib may be safe for use in newborns and children. 9 , 5

Differences

The effectiveness of larotrectinib may vary depending on the type of tumor and the patient. 16 , 9 , 8 , 14 Side effects of larotrectinib may vary between patients. 17 The dosage and duration of larotrectinib treatment may vary between patients. 15

Consistency and Contradictions of Results

Many studies have shown that larotrectinib is effective against NTRK fusion-positive tumors. However, the effectiveness and side effects of larotrectinib may vary depending on the type of tumor and the patient. Further research is needed. 16 , 9 , 6 , 15 , 8 , 17 , 7 , 4 , 3 , 14 , 13 , 5 , 1 , 10 , 2 , 18 , 12 , 19 , 11

Real-World Application Considerations

Larotrectinib can be an effective treatment option for patients with NTRK fusion-positive tumors. However, it is important to use larotrectinib appropriately under the guidance of a physician because it may not be effective for all patients and may cause side effects. 16 , 9 , 6 , 15 , 8 , 17 , 7 , 4 , 3 , 14 , 13 , 5 , 1 , 10 , 2 , 18 , 12 , 19 , 11

Limitations of Current Research

The effectiveness and safety of larotrectinib have not been fully evaluated in all patients. 16 , 9 , 6 , 15 , 8 , 17 , 7 , 4 , 3 , 14 , 13 , 5 , 1 , 10 , 2 , 18 , 12 , 19 , 11 There is not enough data on the long-term effects and side effects of larotrectinib. 16 , 9 , 6 , 15 , 8 , 17 , 7 , 4 , 3 , 14 , 13 , 5 , 1 , 10 , 2 , 18 , 12 , 19 , 11

Future Research Directions

Further research is needed on the efficacy and safety of larotrectinib. More data is needed, especially regarding the long-term effects and side effects of larotrectinib, its effectiveness in various tumors and patients, and its combined effects with other therapies. 16 , 9 , 6 , 15 , 8 , 17 , 7 , 4 , 3 , 14 , 13 , 5 , 1 , 10 , 2 , 18 , 12 , 19 , 11

Conclusion

Larotrectinib has the potential to be an effective treatment option for patients with NTRK fusion-positive tumors. However, it is important to use larotrectinib appropriately under the guidance of a physician because it may not be effective for all patients and may cause side effects. 16 , 9 , 6 , 15 , 8 , 17 , 7 , 4 , 3 , 14 , 13 , 5 , 1 , 10 , 2 , 18 , 12 , 19 , 11 Further research is needed on the efficacy and safety of larotrectinib. 16 , 9 , 6 , 15 , 8 , 17 , 7 , 4 , 3 , 14 , 13 , 5 , 1 , 10 , 2 , 18 , 12 , 19 , 11