The efficacy and safety of selective RET inhibitors in RET fusion-positive non-small cell lung cancer: a meta-analysis

Ke, Jun-yi; Huang, Shu; Jing, Zhi-tao; Duan, Min-chao

doi:10.1007/s10637-023-01390-3

Cited by 3 publications

(1 citation statement)

References 40 publications

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“…In our study, the findings associated with the clinical outcomes related to the TTD, TTP, TTNT-D, and ORR favoring selpercatinib versus standard therapies or MKIs also support selpercatinib’s role as the frontline therapy for RET -activated NSCLC and MTC. Evidence from clinical studies and a recent meta-analysis have demonstrated selpercatinib’s safety in patients with RET fusion-positive aNSCLC [ 25 , 26 , 27 ]. In these studies, the occurrence of treatment-related adverse events as well as treatment discontinuation was lower with selpercatinib.…”

Section: Discussionmentioning

confidence: 99%

Comparative Effectiveness of First-Line Selpercatinib versus Standard Therapies in Patients with RET-Activated Cancers: An Exploratory Interpatient Analysis of LIBRETTO-001

De Braud,

Deschler-Baier,

Morris

et al. 2023

Cancers

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Selpercatinib is indicated for locally advanced/metastatic RET-activated solid tumors after progression or following prior systemic therapies. Until the recently published data from LIBRETTO-431 and LIBRETTO-531, there were limited effectiveness data comparing selpercatinib with other first-line treatments in RET-activated non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC), and thyroid cancer (TC). This study analyzed patient data from LIBRETTO-001 and compared the outcomes (time to treatment discontinuation {TTD}, time to next treatment or death {TTNT-D}, time to progression {TTP}, and the objective response rate {ORR}) of first-line selpercatinib (selpercatinib arm) use with the outcomes of first-line standard therapies in patients who then received selpercatinib in later lines of treatment (comparator arm). Overall, the first-line selpercatinib arm had a longer TTD, TTNT-D, and TTP versus the first-line comparator arm. The hazard ratios (HRs) for TTD were 0.29 (NSCLC), 0.15 (MTC), 0.08 (TC); for TTNT-D, the HRs were 0.48 (NSCLC), 0.11 (MTC), 0.09 (TC); and for TTP, the HRs were 0.54 (NSCLC), 0.15 (MTC), and 0.12 (TC). The ORR was higher for first-line selpercatinib versus the first-line comparator (NSCLC: 85.3% vs. 39.7%; MTC: 82.6% vs. 15.2%; and TC: 81.8% vs. 31.8%). First-line selpercatinib use is associated with improved outcomes compared to first-line comparator therapies for patients with advanced/metastatic RET-activated cancers.

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Section: Discussionmentioning

confidence: 99%

Comparative Effectiveness of First-Line Selpercatinib versus Standard Therapies in Patients with RET-Activated Cancers: An Exploratory Interpatient Analysis of LIBRETTO-001

De Braud,

Deschler-Baier,

Morris

et al. 2023

Cancers

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Cardiovascular toxicities of selective ret-specific tyrosine kinase inhibitors: a pharmacovigilance study based on the United States Food and Drug Administration Adverse Event Reporting System database

Hou,

Ren,

Chen

et al. 2024

Expert Opinion on Drug Safety

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Adverse event profile differences between pralsetinib and selpercatinib: a real-world study based on the FDA adverse events reporting system

Jie,

Li,

Jing

et al. 2024

Front. Pharmacol.

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AimsThe objective of this study is to compare the adverse events (AEs) associated with pralsetinib and selpercatinib.MethodsTo evaluate the imbalance of AEs linked to pralsetinib and selpercatinib in real-world data, the reporting odds ratio (ROR) was utilized to detect potential signals of AEs. Stratified analysis was conducted to examine the differences in AEs occurring among different genders and age groups taking pralsetinib and selpercatinib.ResultsFAERS received 891 reports for pralsetinib and 569 reports for selpercatinib. Our analysis confirmed expected AEs like hypertension, fatigue, and elevated transaminase levels. Unexpected AEs such as rhabdomyolysis, myocardial injury and cognitive disorder were associated with pralsetinib, while selpercatinib was linked with pulmonary embolism, deep vein thrombosis, and pericardial effusion. The risk of AEs such as decreased platelet count, anemia, decreased white blood cell count, pneumonitis, asthenia, and edema caused by pralsetinib is significantly higher than that of selpercatinib. In contrast, the risk of AEs such as ascites, elevated alanine aminotransferase, and elevated aspartate aminotransferase caused by selpercatinib is significantly higher than that of pralsetinib. Women treated with pralsetinib experience higher rates of hypertension, pulmonary embolism, and blurred vision than men, who are more susceptible to rhabdomyolysis. Adults between 18 and 65 years are more likely to experience taste disorder, edema, and pulmonary embolism than individuals older than 65, who are particularly vulnerable to hypertension. For patients treated with selpercatinib, males demonstrate a significantly higher incidence of QT prolongation, urinary tract infection, and dysphagia. Individuals aged 18 to 65 are more likely to experience pyrexia and pleural effusion than those older than 65, who are more prone to hypersensitivity.ConclusionIn the clinical administration of pralsetinib and selpercatinib, it is crucial to monitor the effects of gender and age on AEs and to be vigilant for unlisted AEs.

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The efficacy and safety of selective RET inhibitors in RET fusion-positive non-small cell lung cancer: a meta-analysis

Cited by 3 publications

References 40 publications

Comparative Effectiveness of First-Line Selpercatinib versus Standard Therapies in Patients with RET-Activated Cancers: An Exploratory Interpatient Analysis of LIBRETTO-001

Comparative Effectiveness of First-Line Selpercatinib versus Standard Therapies in Patients with RET-Activated Cancers: An Exploratory Interpatient Analysis of LIBRETTO-001

Cardiovascular toxicities of selective ret-specific tyrosine kinase inhibitors: a pharmacovigilance study based on the United States Food and Drug Administration Adverse Event Reporting System database

Adverse event profile differences between pralsetinib and selpercatinib: a real-world study based on the FDA adverse events reporting system

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