Cancer symptom response as an oncology clinical trial end point

Abstract

Introduction: A critical challenge in oncology is interpreting clinical trial results to inform clinical decision making. Clinical trials typically focus on overall survival (OS) and progression-free survival (PFS) as primary endpoints, which do not reflect early signs of meaningful patient benefit or harm. Cancer symptom response (CSR) can provide information about early treatment response, and studies show that CSR predicts long-term health outcomes. Areas covered: CSR requires careful consideration of its measurement and interpretation to facilitate integration into clinical practice. We describe considerations for the evaluation, analysis, and interpretation of CSR in clinical trials. To illustrate the potential clinical value of CSR, we performed a retrospective analysis of a three-arm randomized cooperative-group clinical trial. Expert commentary: Evaluation of CSR provides a meaningful assessment of early cancer treatment effects. It can act as an early signal of disease progression and death and thus can identify which patients with stable disease will have a more favorable prognosis. Future research will include development of methods for more accurate assessment of CSR, reduction of the number of symptoms used as signals for disease progression or survival by tumor type, and statistical methods that effectively correct for missing data and informative censoring.

An Unsupervised Machine Learning Approach to Evaluating the Association of Symptom Clusters With Adverse Outcomes Among Older Adults With Advanced Cancer

“…This suggests that assessment of symptom burden prior to treatment initiation contributes clinically useful prognostic information for treatment decision-making among older adults. Because of the expected limited survival in this population, baseline symptom burden could be more clinically meaningful for estimating outcomes than the response to treatment, the traditional oncology clinical trial end point …”

Association of Perceived Benefit or Burden of Research Participation With Participants’ Withdrawal From Cancer Clinical Trials

“… 15 The experimental medicines used in CCTs can create life-restricting fatigue, sickness or retching, and other adverse effects. 16 Moreover, cancer itself can cause neuropathies, pain, and psychological distress, among other events. 16 , 17 However, we found that perceived benefits of research participation were important to all patients and were a factor in trial retention, even in the face of many perceived burdens.…”

Development of a Functional Assessment of Chronic Illness Therapy item library and primary symptom list for the assessment of patient-reported adverse events associated with immune checkpoint modulators

“…PROs are defined as "any report of the status of a patient's (or person's) health condition, health behavior, or experience with healthcare that comes directly from the patient, without interpretation of the patient's response by a clinician or anyone else" [17] . In clinical trials, PROs enhance understanding of treatment toxicity, HRQOL, and treatment value [18][19][20][21][22] . In clinical practice, PROs aid early symptom detection, symptom management, and treatment decision making [23][24][25][26][27] .…”