Table1_Post-marketing safety evaluation of lurbinectedin: a pharmacovigilance analysis based on the FAERS database.DOCX

Background: On 15 June 2020, the United States Food and Drug Administration (FDA) approved lurbinectedin for treating adult patients with metastatic small-cell lung cancer whose disease has progressed despite prior platinum-based chemotherapy. Following its market approval, safety data on lurbinectedin in large populations is currently lacking. Therefore, this study aims to evaluate adverse events (AEs) associated with lurbinectedin using the FDA’s Adverse Event Reporting System (FAERS)database.Methods: Data concerning lurbinectedin from the FAERS database were extracted for the period from June 2020 to September 2023. Four disproportionality analysis algorithms were utilized to assess potential AEs linked to lurbinectedin: reporting odds ratio (ROR), proportional reporting ratio, disproportionate multi-item gamma Poisson shrinker, and Bayesian confidence propagation neural network. These algorithms were applied to quantify signals of lurbinectedin-related AEs.Result: A total of 5,801,535 AE reports were retrieved from the FAERS database, with 511 related to lurbinectedin. These lurbinectedin-induced AEs were observed in 23 system organ classes (SOCs). After simultaneously applying the four algorithms, 47 lurbinectedin-induced AE signals were detected in 23 SOCs. At the SOC level, blood and lymphatic system disorders (ROR, 6.70; 95% confidence interval [CI]: 5.47–8.22) were the only SOC that met all four algorithms. Lurbinectedin’s most frequent adverse event was death (ROR: 6.11%, 95% CI: 4.86–7.68), while extravasation exhibited the strongest signal intensity in the ROR algorithm (ROR: 326.37%, 95% CI: 191.66–555.75). Notably, we identified a novel signals: tumor lysis syndrome (ROR: 63.22%, 95% CI: 33.87–117.99). The mean time of onset of AEs was 66 days, the median time of onset was 25 days (interquartile range: 8–64 days), and most AEs occurred within the first month of lurbinectedin treatment.Conclusion: Our study provided a comprehensive evaluation of lurbinectedin’s safety profile in the post-marketing setting. In addition to the adverse events consistent with the existing clinical trials and labeling information, we have also identified an unreported signal related to tumor lysis syndrome. This finding will better guide the clinical practice of lurbinectedin and provide valuable evidence for future research.</p

DataSheet1_Post-marketing safety evaluation of lurbinectedin: a pharmacovigilance analysis based on the FAERS database.ZIP

Background: On 15 June 2020, the United States Food and Drug Administration (FDA) approved lurbinectedin for treating adult patients with metastatic small-cell lung cancer whose disease has progressed despite prior platinum-based chemotherapy. Following its market approval, safety data on lurbinectedin in large populations is currently lacking. Therefore, this study aims to evaluate adverse events (AEs) associated with lurbinectedin using the FDA’s Adverse Event Reporting System (FAERS)database.Methods: Data concerning lurbinectedin from the FAERS database were extracted for the period from June 2020 to September 2023. Four disproportionality analysis algorithms were utilized to assess potential AEs linked to lurbinectedin: reporting odds ratio (ROR), proportional reporting ratio, disproportionate multi-item gamma Poisson shrinker, and Bayesian confidence propagation neural network. These algorithms were applied to quantify signals of lurbinectedin-related AEs.Result: A total of 5,801,535 AE reports were retrieved from the FAERS database, with 511 related to lurbinectedin. These lurbinectedin-induced AEs were observed in 23 system organ classes (SOCs). After simultaneously applying the four algorithms, 47 lurbinectedin-induced AE signals were detected in 23 SOCs. At the SOC level, blood and lymphatic system disorders (ROR, 6.70; 95% confidence interval [CI]: 5.47–8.22) were the only SOC that met all four algorithms. Lurbinectedin’s most frequent adverse event was death (ROR: 6.11%, 95% CI: 4.86–7.68), while extravasation exhibited the strongest signal intensity in the ROR algorithm (ROR: 326.37%, 95% CI: 191.66–555.75). Notably, we identified a novel signals: tumor lysis syndrome (ROR: 63.22%, 95% CI: 33.87–117.99). The mean time of onset of AEs was 66 days, the median time of onset was 25 days (interquartile range: 8–64 days), and most AEs occurred within the first month of lurbinectedin treatment.Conclusion: Our study provided a comprehensive evaluation of lurbinectedin’s safety profile in the post-marketing setting. In addition to the adverse events consistent with the existing clinical trials and labeling information, we have also identified an unreported signal related to tumor lysis syndrome. This finding will better guide the clinical practice of lurbinectedin and provide valuable evidence for future research.</p

The participants’ view in the VR, 3D, and 2D conditions.

(A) An example screenshot of the view for participants in the VR condition. Specifically, this showcases the participant’s view at the beginning of each trial. No stimulus features are visible. (B) An example screenshot from the 3D condition showing the participant’s point of view during the feedback phase. Participant’s choice shown in red, correct answer shown in green. Participant’s choice lights up in green if they answered correctly. (C) The 2D stimulus as presented to the 2D group. Symbols and category structure are the same across all three conditions.</p

Accuracy and response time results.

(A) Accuracy as a proportion and (B) response times across the 10 bins, measured in milliseconds, by condition.</p

Fixation counts and average fixation durations.

(A) Number of fixations per trial averaged for each bin, by condition. (B) Average fixation length in milliseconds for each bin, by condition.</p

Example stimulus features and category structure.

Each of the four categories can be uniquely determined from the value of features 1 and 2, while feature 3 has no bearing on the category. Optimal information sampling is thus viewing features 1 and 2, and ignoring feature 3.</p

A graphical representation of a stimulus cube.

The stimulus cube initially spawns in a position where none of the three features can be seen. By rotating the cube each of the three features can be seen in turn. The wells prevent more than one feature from being visible at a time. Note that opposing sides of the cube display the same feature.</p

The controllers used to make responses in each condition.

(A) Image of the Logitech F310 controller used in the 2D and 3D conditions (B) Image of the HTC Vive hand controllers used in the VR condition.</p

The axis angle is calculated to reveal which feature is in view.

The participant rotates the cube about a central point. As the cube is rotated relative to the position of the participant view, features are exposed inside the wells. As the cube is rotated, the axis angle changes. This can be used to determine when a feature is visible to the viewer. At 56 degrees of rotation, the feature begins to be viewable to the participant.</p

Attentional optimization and feedback duration by condition.

(A) Information access optimization ranging from -1 to 1 (see text for calculation) and (B) time spent looking at feedback in between trials across 10 bins, measured in milliseconds, by condition.</p