An evaluation of selinexor's clinical trial portfolio: a cross-sectional study.

Abstract

Background: 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 the clinical trial portfolio of selinexor.

Objectives: This investigation aims to evaluate published clinical trials of selinexor to assess its risk/benefit in terms of response and survival outcomes as well as its toxicity.

Design: Cross-sectional.

Methods: We conducted a cross-sectional investigation by searching databases for published clinical trials that used a response criteria pertaining to selinexor administration in adults. In a masked, duplicate manner, we extracted trial characteristics, median progression-free survival (PFS), overall survival (OS), objective response rates (ORR), and Grade 3-5 adverse events (AEs).

Results: Of the 753 articles identified, 40 were included in our final sample. The trials reporting PFS data using control arms showed a median difference in PFS by 4.4 months, favoring the selinexor treatment arm. However, trials that reported OS data with control arms indicated that selinexor showed a worse median difference in OS (-2.4 months) than the control arms. Among the 53 measurements reporting ORR, the weighted median ORR was 36.4%, and the median difference ORR (4.8%) favored selinexor. Additionally, 4153 cumulative Grade 3-5 AEs were reported.

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 pretest probability. Our risk/benefit analysis of selinexor provides valuable insight into the unfavorable outcomes of the drug and increased high-grade AEs. Hence, further testing of selinexor should be carefully scrutinized and contextualized with the portfolio of data we present.