Side Effects of selpercatinib: A Synthesis of Findings from 6 Studies

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Original Abstract of the Article

Main Research Findings

Selpercatinib is a promising new treatment for cancers with RET gene abnormalities, such as RET fusion-positive non-small cell lung cancer and RET mutation-positive medullary thyroid cancer. 3 , 4 , 2 These studies have shown that selpercatinib has effective antitumor activity and is well tolerated. 1 Selpercatinib has demonstrated high efficacy and safety in patients with RET fusion-positive non-small cell lung cancer, RET mutation-positive medullary thyroid cancer, and RET fusion-positive thyroid cancer. 4

Reasons for Side Effects

Selpercatinib is a drug that inhibits RET kinase. RET kinase plays a critical role in cell growth and proliferation. Therefore, inhibiting RET kinase is expected to suppress cell growth and proliferation, thereby suppressing the growth of cancer cells. However, RET kinase is also present in normal cells, so selpercatinib can affect normal cells and cause side effects. 6

Common Side Effects

Hypertension

Hypertension is a common side effect of selpercatinib. 4 , 1 It is believed to be caused by the inhibition of RET kinase by selpercatinib. 6

Elevated Liver Function Tests

Elevated liver function tests have been reported as a side effect of selpercatinib. 4 , 1 Elevated liver function tests may indicate that selpercatinib is affecting the liver. 6

QT Prolongation

QT prolongation has been reported as a side effect of selpercatinib. 1 QT prolongation is caused by abnormal electrical activity of the heart. 6

Neutropenia

Neutropenia has been reported as a side effect of selpercatinib. 1 Neutropenia is caused by a decrease in the number of white blood cells. 6

Pneumonitis

Pneumonitis has been reported as a side effect of selpercatinib. 1 Pneumonitis is caused by inflammation of the lungs. 6

Chylous Ascites

Chylous ascites has been reported as a possible rare side effect of selpercatinib. Chylous ascites is caused by lymph fluid accumulating in the abdominal cavity. 6

Side Effects Management

Hypertension

If hypertension occurs, antihypertensive medications need to be taken according to the doctor's instructions. 4 , 1

Elevated Liver Function Tests

If elevated liver function tests are observed, the doctor's instructions need to be followed to monitor liver function. 4 , 1 If liver function tests are abnormal, selpercatinib administration may be temporarily discontinued. 6

QT Prolongation

If QT prolongation is observed, the doctor's instructions need to be followed to monitor the electrical activity of the heart. 1 If QT prolongation worsens, it may lead to serious cardiac events such as ventricular fibrillation. 6

Neutropenia

If neutropenia is observed, the doctor's instructions need to be followed to monitor the white blood cell count. 1 If neutropenia worsens, the risk of infection increases. 6

Pneumonitis

If pneumonitis is observed, appropriate treatment should be received according to the doctor's instructions. 1 6

Comparison Among Studies

Commonalities Among Studies

All of these studies have shown that selpercatinib is highly effective and safe for cancer patients with RET gene abnormalities. 3 , 4 , 2 , 5 , 1

Differences Among Studies

These studies differ in the types of cancer targeted and the research design. 3 , 4 , 2 , 5 , 1 For example, LIBRETTO-432 is a phase III trial targeting stage IB-IIIA RET fusion-positive non-small cell lung cancer. 3 LIBRETTO-531 is a phase III trial targeting multikinase inhibitor-naive RET mutation-positive medullary thyroid cancer. 2

Cautions Regarding Real-World Application

Selpercatinib may be an effective treatment for cancer patients with RET gene abnormalities, but there is also a risk of side effects. 3 , 4 , 2 , 5 , 1 When considering taking selpercatinib, it is necessary to consult with a doctor and make a decision after fully understanding the risks and benefits. 6

Limitations of Current Research

Further research is needed to assess the long-term safety and efficacy of selpercatinib. 3 , 4 , 2 , 5 , 1

Future Research Directions

Further clinical trials are needed to evaluate the long-term safety and efficacy of selpercatinib. 3 , 4 , 2 , 5 , 1 It is also necessary to evaluate the effectiveness of selpercatinib for cancers with other types of RET gene abnormalities. 6

Conclusion

Selpercatinib is a promising treatment for cancers with RET gene abnormalities. 3 , 4 , 2 , 5 , 1 However, there is also a risk of side effects. 3 , 4 , 2 , 5 , 1 When considering taking selpercatinib, it is necessary to consult with a doctor and make a decision after fully understanding the risks and benefits. 6

Literature analysis of 6 papers
Positive Content
6
Neutral Content
0
Negative Content
0
Article Type
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0
1
4
6
1.

Efficacy and Safety of RET-Specific Kinase Inhibitors in RET-Altered Cancers: A Systematic Review.

Author: AliMuhammad Ashar, ShahSyed S, AliRimsha, BajwaShammas Farooq, RehmanSana, AnwarAqsa, AnwarMuhammad Yasir, SaeedMemoona, MirzaNayab, AimanWajeeha

RET-altered tumor treatment
ALT changes
Hypertension
Neutropenia
Pneumonitis
QT prolongation

Selpercatinib and pralsetinib are the only FDA-approved RET-specific tyrosine kinase inhibitors for RET-altered tumors. This review summarizes the efficacy and safety of these drugs based on a comprehensive literature search. Objective response rates were 60-89%, and ≥Grade 3 adverse events were reported in 28-53% of patients.

Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

2.

LIBRETTO-531: a phase III study of selpercatinib in multikinase inhibitor-na&#239;ve <i>RET</i>-mutant medullary thyroid cancer.

Author: WirthLori J, BroseMarcia S, EliseiRossella, CapdevilaJaume, HoffAna O, HuMimi I, TaharaMakoto, RobinsonBruce, GaoMing, XiaMeng, MaedaPatricia, ShermanEric

Antitumor activity

Selpercatinib is a new drug that targets RET kinase, which is a protein that can cause cancer. In a clinical trial, selpercatinib showed promising results in treating patients with RET-mutant medullary thyroid cancer (MTC). The drug was effective in shrinking tumors and had manageable side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

3.

LIBRETTO-432, a phase III study of adjuvant selpercatinib or placebo in stage IB-IIIA <i>RET</i> fusion-positive non-small-cell lung cancer.

Author: TsuboiMasahiro, GoldmanJonathan W, WuYi-Long, JohnsonMelissa L, Paz-AresLuis, YangJames Chih-Hsin, BesseBenjamin, SuWeiji, ChaoBo H, DrilonAlexander

Manageable toxicity
RET inhibitor efficacy

Selpercatinib, a RET kinase inhibitor, demonstrated promising efficacy in treating advanced/metastatic RET fusion-positive non-small-cell lung cancer (NSCLC) with manageable side effects. A phase III trial is evaluating its use in earlier stages.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

5.

Lung cancer treated abroad with receptor tyrosine kinase inhibitor.

Author: EideInger Johanne Zwicky, BrustugunOdd Terje

Radiological response
Symptom relief

This case presentation describes a patient with advanced lung adenocarcinoma who was diagnosed with a KIF5B-RET fusion after progression on initial treatment. The patient received pralsetinib through a compassionate use program and experienced symptom relief within weeks and a radiological partial response after two months of treatment. This case highlights the importance of next-generation sequencing (NGS) in identifying patients who might benefit from targeted therapies.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : Norwegian

6.

ESMO recommendations on the standard methods to detect RET fusions and mutations in daily practice and clinical research.

Author: BelliC, Penault-LlorcaF, LadanyiM, NormannoN, ScoazecJ-Y, LacroixL, Reis-FilhoJ S, SubbiahV, GainorJ F, EndrisV, RepettoM, DrilonA, ScarpaA, AndréF, DouillardJ-Y, CuriglianoG

Durable antitumor activity
Manageable toxicity profiles
Off-target toxicities

Selpercatinib, a new selective RET inhibitor, has recently been approved by the FDA for the treatment of RET-altered tumors. Clinical trials have shown marked and durable antitumour activity and manageable toxicity profiles in patients with RET-altered tumors.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

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