Figure - available from: Frontiers in Oncology
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Schematic representation of ANK3-RET fusion detected. Both genes are located on chromosome 10 (upper graph). The detected fusion occurs as depicted in central graph linking ANK3 (exon 1-33) to RET (exon 12-20) given a chimeric protein (below). Breakpoint area is enlarge showing nucleotide sequence and coding aminoacids.
Source publication
Over the past decade, molecular characterization has led to change the management of advanced non-small cell lung cancer (NSCLC) harboring driver mutations. Rearranged during transfection (RET) gene fusions, occurring in 1% to 2% of NSCLC, have emerged as an oncogenic druggable target. Systemic targeted therapies with highly selective RET inhibitor...
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Citations
... In a phase I/II trial, the dose of selpercatinib ranged from 20 mg once daily to 240 mg twice daily, and 160 mg twice daily was determined as the recommended dose. Although one case report of RET-rearranged patient, the dosage of selepercatinib was modified to 160 mg in the morning and 80 mg at night due to its toxicity and showed efficacy [9], this is the first report of a therapeutic effect at such a low dose of selpercatinib as in our case. Moreover, the intracranial response rate of selpercatinib was more than 80 % in both untreated and treated patients [10,11]. ...
Chromosomal rearrangements of the RET (rearranged during transfection) gene are detected in approximately 1–2% of non-small cell lung cancers (NSCLC) and have function as oncogenic driver genes. Selpercatinib is a highly effective RET inhibitor for RET-rearranged patients with NSCLC and shows mostly tolerable adverse events. However, hypertension, aspartate aminotransferase increase, and alanine aminotransferase increase are the most common adverse events, and dose modification or discontinuation is required occasionally. Here, we describe a case who has response to 40 mg of selpercatinib every other day because the dose had to be adjusted owing to adverse events such as liver dysfunction. Dose modification of selpercatinib, according to adverse event incidences, may be considered, as selpercatinib may be effective in some cases even at very low concentrations.
... While the development of selpercatinib has improved survival, with its increasing use, it is crucial to be aware of AEs [17]. Currently, clinical trials have revealed the most prevalent AEs of selpercatinib, including edema, diarrhea, fatigue, dry mouth, abdominal pain, constipation, hypertension, rash, nausea, and headache [18]. ...
... Therefore, doses such as 60 mg and 180 mg are not permitted. In a case involving a 43-year-old advanced non-small cell lung cancer patient diagnosed with a rare RET gene fusion, a modified selpercatinib dosage (160 mg in the morning and 80 mg in the evening) was used with good tolerance and without compromising effectiveness [17]. This case suggests that in certain situations, a modified selpercatinib dosage outside the label (such as using different doses in the morning and evening) may provide a safe and effective alternative, rather than crushing or chewing it. ...
Background
Selpercatinib, a highly selective tyrosine kinase inhibitor, has emerged as an excellent treatment option for patients with rearranged during transfection-altered cancer. However, there is limited comprehensive safety information available for selpercatinib through large-scale post-marketing monitoring.
Methods
This study conducted a comprehensive analysis of selpercatinib-related adverse events (AEs) using the FDA Adverse Event Reporting System database. Four disproportionality methods were employed to identify potential AEs associated with selpercatinib. Specifically, this study investigated the differences in AEs of selpercatinib with respect to reporter continent, indication, sex, age, weight, dose, frequency, and onset time.
Results
A total of 464 reports and 1,007 selpercatinib-related AEs were identified. Three new significant AEs were discovered, including dysphagia, pericardial effusion, and hemiparesis. Notably, Asia reported hepatic function abnormal more frequently, especially in patient administered doses exceeding 160 mg. Furthermore, hypersensitivity was reported more frequently by Asia and in individuals weighing less than 50 kg.
Conclusions
It is paramount to stay vigilant concerning the potential emergence of three newly identified AEs. Significant differences were found in selpercatinib-related AEs concerning reporter continent, sex, weight, dose, frequency, and onset time, which deserved clinical attention. These findings contribute to a broader understanding of the AE profiles of selpercatinib.
