Background:
In clinical trials, the current reporting approach for adverse events (AEs) focuses on the “worst grade” experienced over the entire treatment course. In recurrent ovarian cancer (ROC), potential side-effects influence patients’ decisions about undergoing treatment. Current reporting approaches do not provide information whether AEs are likely to worsen, improve, or remain constant over time.
Patients and Methods:
Non-hematologic (NH) adverse event (AE) data was extracted from the CALYPSO trial that compared carboplatin with pegylated liposomal doxorubicin (CD) to carboplatin with paclitaxel (CP) in ROC. Generalized estimating equations (GEE) were used to assess the trend in combined Grade 2 or higher (G2+) AE and in each specific AE. Risk of G2+ AE for each treatment arm was also determined.
Results:
Risk of combined G2+ AE increased with CP (4.1% per cycle) but decreased with CD (0.8%, P <0.01). When alopecia and sensory neuropathy were excluded, risk of G2+ AE decreased by 2.7% per cycle (P <0.01) for both treatment arms with no significant difference between them (P = 0.53). G2+ nausea improved (15.2% per cycle, P <0.01) but 60% more likely in the CD arm (P < 0.01). G2+ sensory neuropathy worsened (29.3% per cycle, P <0.01) and higher risk with CP (83.7% per cycle, P < 0.01). Fatigue was stable through treatment (P =0.06) with no difference between treatment arms (P =0.19). G2+ pain decreased over time (13.4% per cycle, P <0.01) but no difference between treatment arms (P =0.54)
Conclusion:
Trends in AE over treatment should be evaluated in clinical trial AE reporting as illustrated here for ROC. These data have the potential to aid patients in treatment choices and to optimize the management of AE, and is of particular relevance for novel treatments with limited clinical experience.