A phase 1b trial of selinexor, a first-in-class selective inhibitor of nuclear export (SINE), in combination with doxorubicin in patients with advanced soft tissue sarcomas (STS)

Lewin, Jeremy; Malone, Eoghan Ruadh; Al-Ezzi, Esmail Mutahar; Fasih, Samir; Pedersen, Pernille; Accardi, Sarah; Gupta, Abha; Razak, Albiruni Abdul

doi:10.1016/j.ejca.2020.10.032

Cited by 10 publications

(6 citation statements)

References 24 publications

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“…Another study evaluated the safety of selinexor in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), including subtypes of NHL such as diffuse large B-cell lymphoma, Richter transformation, mantle cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia 38 . Additionally, Lewin’s study explored the safety and efficacy of selinexor in combination with doxorubicin in treating advanced soft tissue sarcomas (STS), compassing malignant peripheral nerve sheath tumors (n = 3) and other types of sarcomas (n = 16) 39 . According to these results, selinexor has shown certain effectiveness in treating various solid tumors as a potential indication.…”

Section: Discussionmentioning

confidence: 99%

Adverse events reporting of XPO1 inhibitor - selinexor: a real-word analysis from FAERS database

Liu,

Yang,

Feng

et al. 2024

Sci Rep

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As the world's first oral nuclear export inhibitor, selinexor is increasingly being used in clinical applications for malignant tumors. However, there is no extensive exploration on selinexor's adverse events (ADEs), necessitating a real-word assessment of its clinical medication safety. FAERS data (July 2019–June 2023) were searched for selinexor ADE reports across all indications. Use the system organ class (SOC) and preferred terms (PT) from the medical dictionary for regulatory activities (MedDRA) to describe, categorize, and statistic ADEs. Disproportionality analysis was employed through calculation of reporting odds ratio (ROR) and proportional reporting ratio (PRR). Based on total of 4392 selinexor related ADE reports as the primary suspect (PS), of which 2595 instances were severe outcomes. The predominant ADEs included gastrointestinal disorders, myelosuppression symptoms, and various nonspecific manifestations. 124 signals associated with selinexor ADE were detected, and 10 of these top 15 signals were not included into the instructions. Our study provides real-world evidence regarding the drug safety of selinexor, which is crucial for clinicians to safeguard patients’ health.

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Section: Discussionmentioning

confidence: 99%

Adverse events reporting of XPO1 inhibitor - selinexor: a real-word analysis from FAERS database

Liu,

Yang,

Feng

et al. 2024

Sci Rep

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“…In a phase Ib trial (NCT03042819), selinexor was tested in combination with adriamycin for treating patients with advanced soft tissue sarcoma. 245 A total of 25 patients were included in the trial. Eighty percent of these patients experienced grade 3 or higher treatment-related adverse events (AEs).…”

Section: Sarcomamentioning

confidence: 99%

“…In a phase Ib trial (NCT03042819), selinexor was tested in combination with adriamycin for treating patients with advanced soft tissue sarcoma 245 . A total of 25 patients were included in the trial.…”

Section: Clinical Trials Of Xpo1 Inhibitorsmentioning

confidence: 99%

The nuclear export protein exportin‐1 in solid malignant tumours: From biology to clinical trials

Lai,

Xu,

Dai

2024

Clinical & Translational Med

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BackgroundExportin‐1 (XPO1), a crucial protein regulating nuclear‐cytoplasmic transport, is frequently overexpressed in various cancers, driving tumor progression and drug resistance. This makes XPO1 an attractive therapeutic target. Over the past few decades, the number of available nuclear export‐selective inhibitors has been increasing. Only KPT‐330 (selinexor) has been successfully used for treating haematological malignancies, and KPT‐8602 (eltanexor) has been used for treating haematologic tumours in clinical trials. However, the use of nuclear export‐selective inhibitors for the inhibition of XPO1 expression has yet to be thoroughly investigated in clinical studies and therapeutic outcomes for solid tumours.MethodsWe collected numerous literatures to explain the efficacy of XPO1 Inhibitors in preclinical and clinical studies of a wide range of solid tumours.ResultsIn this review, we focus on the nuclear export function of XPO1 and results from clinical trials of its inhibitors in solid malignant tumours. We summarized the mechanism of action and therapeutic potential of XPO1 inhibitors, as well as adverse effects and response biomarkers.ConclusionXPO1 inhibition has emerged as a promising therapeutic strategy in the fight against cancer, offering a novel approach to targeting tumorigenic processes and overcoming drug resistance. SINE compounds have demonstrated efficacy in a wide range of solid tumours, and ongoing research is focused on optimizing their use, identifying response biomarkers, and developing effective combination therapies.Key Points Exportin‐1 (XPO1) plays a critical role in mediating nucleocytoplasmic transport and cell cycle. XPO1 dysfunction promotes tumourigenesis and drug resistance within solid tumours. The therapeutic potential and ongoing researches on XPO1 inhibitors in the treatment of solid tumours. Additional researches are essential to address safety concerns and identify biomarkers for predicting patient response to XPO1 inhibitors.

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“…In the realm of soft tissue sarcoma (STS), Selinexor's combination with doxorubicin has yielded partial remission in 21% of patients, and stable disease in 63% (16,17). This finding is significant, particularly for a diverse and rare cancer like STS, highlighting Selinexor's capacity to fill therapeutic gaps where targeted options are limited.…”

Section: Selinexor In Nonhematologic Malignanciesmentioning

confidence: 99%

Beyond oncology: Selinexor’s journey into anti-inflammatory treatment and long-term management

Li,

Fang,

Zhang

et al. 2024

Front. Immunol.

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Selinexor, a selective inhibitor of nuclear export (SINE), is gaining recognition beyond oncology for its potential in anti-inflammatory therapy. This review elucidates Selinexor’s dual action, highlighting its anti-tumor efficacy in various cancers including hematologic malignancies and solid tumors, and its promising anti-inflammatory effects. In cancer treatment, Selinexor has demonstrated benefits as monotherapy and in combination with other therapeutics, particularly in drug-resistant cases. Its role in enhancing the effectiveness of bone marrow transplants has also been noted. Importantly, the drug’s impact on key inflammatory pathways provides a new avenue for the management of conditions like sepsis, viral infections including COVID-19, and chronic inflammatory diseases such as Duchenne Muscular Dystrophy and Parkinson’s Disease. The review emphasizes the criticality of managing Selinexor’s side effects through diligent dose optimization and patient monitoring. Given the complexities of its broader applications, extensive research is called upon to validate Selinexor’s long-term safety and effectiveness, with a keen focus on its integration into clinical practice for a diverse spectrum of disorders.

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A phase 1b trial of selinexor, a first-in-class selective inhibitor of nuclear export (SINE), in combination with doxorubicin in patients with advanced soft tissue sarcomas (STS)

Cited by 10 publications

References 24 publications

Adverse events reporting of XPO1 inhibitor - selinexor: a real-word analysis from FAERS database

Adverse events reporting of XPO1 inhibitor - selinexor: a real-word analysis from FAERS database

The nuclear export protein exportin‐1 in solid malignant tumours: From biology to clinical trials

Beyond oncology: Selinexor’s journey into anti-inflammatory treatment and long-term management

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