Abstract
Objective: The goal of this investigation is to assess selinexor’s potential benefit and harmful toxicities across multiple indications.
Introduction: Cancer drug development is a complex and costly process. Selinexor is a drug that received accelerated approval as a new treatment for relapsed or refractory diffuse-large B-cell lymphoma and multiple myeloma. Despite initially showing promise in treating these conditions, it has shown high-grade toxicity in clinical trials. Hence, an analysis is needed to assess selinexor’s clinical trial portfolio.
Methods: In this cross-sectional review, clinical trials were searched using PubMed/MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov. Studies were considered eligible if they assessed the administration of selinexor in human adults, used response criteria, and were published in English. In a masked, duplicate manner, we extracted trial characteristics, median progression-free survival (PFS) and overall survival (OS), grade 3-5 adverse events (AEs), and objective response rates (ORR). Depending on primary endpoint specificity and drug tolerability, trials were deemed positive, negative, or indeterminate.
Results: Of the 753 articles identified, 40 were included into our final sample. A total of 19 (47.5%) trials were deemed positive, 10 (25.0%) trials were negative, and 11 (27.5%) trials were considered indeterminate. Of the four trials reporting PFS data using control arms, median delta PFS (4.4 months) favored the selinexor treatment arm. However, of the three trials that reported OS data with control arms, selinexor showed a worse median delta OS (-2.4 months) than the control arms. Of the 53 trials that reported ORR, the total median ORR was 29.3%. Of the three trials reporting ORR using control arms, the median delta ORR (4.8%) favored selinexor. Additionally, 3,222 cumulative grade 3-5 AEs were reported, with the most AEs reported in patients with multiple myeloma.
Conclusion: In comparison to a control arm, selinexor increases PFS and induces response, suggesting drug activity. However, acceptable grade 3-5 AEs or improvement of OS was not seen across a single indication, suggesting a poor pre-test probability. Hence, we believe further testing of selinexor should be carefully scrutinized and contextualized with the portfolio of data we present.
Introduction: Cancer drug development is a complex and costly process. Selinexor is a drug that received accelerated approval as a new treatment for relapsed or refractory diffuse-large B-cell lymphoma and multiple myeloma. Despite initially showing promise in treating these conditions, it has shown high-grade toxicity in clinical trials. Hence, an analysis is needed to assess selinexor’s clinical trial portfolio.
Methods: In this cross-sectional review, clinical trials were searched using PubMed/MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov. Studies were considered eligible if they assessed the administration of selinexor in human adults, used response criteria, and were published in English. In a masked, duplicate manner, we extracted trial characteristics, median progression-free survival (PFS) and overall survival (OS), grade 3-5 adverse events (AEs), and objective response rates (ORR). Depending on primary endpoint specificity and drug tolerability, trials were deemed positive, negative, or indeterminate.
Results: Of the 753 articles identified, 40 were included into our final sample. A total of 19 (47.5%) trials were deemed positive, 10 (25.0%) trials were negative, and 11 (27.5%) trials were considered indeterminate. Of the four trials reporting PFS data using control arms, median delta PFS (4.4 months) favored the selinexor treatment arm. However, of the three trials that reported OS data with control arms, selinexor showed a worse median delta OS (-2.4 months) than the control arms. Of the 53 trials that reported ORR, the total median ORR was 29.3%. Of the three trials reporting ORR using control arms, the median delta ORR (4.8%) favored selinexor. Additionally, 3,222 cumulative grade 3-5 AEs were reported, with the most AEs reported in patients with multiple myeloma.
Conclusion: In comparison to a control arm, selinexor increases PFS and induces response, suggesting drug activity. However, acceptable grade 3-5 AEs or improvement of OS was not seen across a single indication, suggesting a poor pre-test probability. Hence, we believe further testing of selinexor should be carefully scrutinized and contextualized with the portfolio of data we present.
| Original language | American English |
|---|---|
| State | Published - 21 Jul 2023 |
| Event | 7th Annual Joint Research Meeting: Biomedical, Biological, Neuroscience, Physiology, Forensics - Tandy Conference Center, Tulsa, United States Duration: 21 Jul 2023 → 21 Jul 2023 |
Conference
| Conference | 7th Annual Joint Research Meeting: Biomedical, Biological, Neuroscience, Physiology, Forensics |
|---|---|
| Abbreviated title | 7th Joint Annual Research Meeting |
| Country/Territory | United States |
| City | Tulsa |
| Period | 21/07/23 → 21/07/23 |