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

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.