A Closer Look at Reporting Toxicities in Cancer Clinical Trials
QoL for patients with cancer is reduced just as much by the accumulation of low-level toxicities as it is from high-level adverse events.
A paramount concern in cancer clinical trials is grade 3/4 adverse events. However, new findings suggest that it may be time to put a greater emphasis on the cumulative effect of multiple low-level toxicities. Research published in the December 2018 issue of JNCCN—Journal of the National Comprehensive Cancer Network has found that quality of life (QoL) for patients with cancer is reduced by an accumulation of low-level toxicities just as much as it is from high-level adverse events. Investigators also found that patient-reported outcomes appear to more likely reflect the impact on a patient's physical well-being than those reported by their physician.
Dutch researchers looked at 184 patients with metastatic castrate-naive prostate cancer who were treated between October 2004 and December 2008 as part of a multicenter phase 3 randomized trial. Each patient completed QoL assessments before treatment, and then again at 3 and 6 months posttreatment. As part of this investigation, separate toxicity data were reported by clinicians and patients.
The researchers found that the strongest impact on QoL came from cumulative toxicities, regardless of the grade. The researchers also found that patient-reported toxicity scores were more associated with QoL outcomes than clinician-reported scores. Study investigator Claudia Schuurhuizen, MD, Amsterdam UMC Cancer Center, The Netherlands, said incorporating patient-reported toxicity into routine cancer care ensures patients get high-quality care with better symptom detection and management.
“Clinicians and patients seem to differ in their evaluation of toxicity and subsequent burden of treatment. The clinical toxicity evaluation mainly focuses on occurrence and severity, while patient-reported toxicity focuses more on the duration and relative burden,” Dr Schuurhuizen told Cancer Therapy Advisor. “A description of severe toxicities by clinicians is important and relevant to determine drug tolerability, while patients themselves may provide a more representative overview of how toxicity throughout therapy — including the recurring, longer-lasting grade 1 or grade 2 AEs — may impact their day-to-day lives.”
For this investigation, the clinicians reported AEs during clinical visits and then calculated the cumulative toxicity scores. The team looked at 385 patients (mean age, 63.5 years), although data from only 184 patients were included. Patient-reported AEs were completed by 168 patients (91.3%) at 3 months posttreatment, and 107 patients (58.2%) at 6 months posttreatment. The researchers found that the clinician-reported all-grade AEs and severity scores were associated with deteriorated physical QoL. The total number of clinician-reported high-grade AEs was not associated with poor physical QoL. But all patient-reported scores were significantly associated with deteriorated physical and global QoL (P <.01 for all). On these findings, the authors of the study wrote, “Although there was no significant association between clinician-reported high-grade cumulative toxicity scores with global and physical QoL, this could have been the result of lack of power instead of lack of effect.”