Lead Investigator: John (Devin) Peipert, Northwestern University
Title of Proposal Research: Study of Functional Assessment of Chronic Illness Therapy (FACIT) GP5 Item as a Measure of Treatment Tolerability in Advanced Cancer Patients across Multiple Tumour Sites and Treatment Types
Vivli Data Request: 7760
Funding Source: This research is funded by a contract from the United States Food and Drug Administration, “Evaluation of a Global Item for Side Effect Bother” (#75F40121C00162; PIs, Peipert and Roydhouse).
Potential Conflicts of Interest: None
Summary of the Proposed Research:
As cancer treatments have become more effective, they have often also become more toxic. Patients’ ability to tolerate treatments in large part determines their success. The traditional standard of tolerability assessment has primarily used clinician-reported data using the Common Terminology Criteria for Adverse Events (CTCAE). Yet, relying only on clinician reports may miss critical aspects of tolerability. While clinician and patient report often align generally, there may be some aspects of symptom experience that clinicians miss. For example, symptoms that are not directly observable such as fatigue and dyspnoea (breathlessness) may be difficult for clinicians to assess accurately. Patients often experience treatment-related symptoms that are not detected by clinicians and have a significant impact on their daily activities and quality of life. Furthermore, patient reports of symptomatic adverse events are more strongly associated with overall health status, while clinician reports predict clinical events like emergency room visits and death. Symptomatic adverse events are simply adverse events that cause symptoms.
To address the potential weaknesses of relying only on clinician reports, there is increasing interest in incorporating patient-reported measures of tolerability in cancer clinical trials. Doing so will help to understand the extent to which symptomatic adverse events affect patients’ ability or desire to adhere to cancer therapies. To advance patient-reported tolerability assessment, a new definition of tolerability has been offered: “The tolerability of a medical product is the degree to which symptomatic and non-symptomatic adverse events associated with the product’s administration affect the ability or desire of the patient to adhere to the dose or intensity of therapy. Non-symptomatic adverse events are adverse events that do not cause symptoms. A complete understanding of tolerability should include direct measurement from the patient on how they are feeling and functioning while on treatment.”
It is important to identify which patient-reported outcomes (PRO) measures best capture this new definition. One likely option includes the patient-reported outcomes (PRO) version of the CTCAE, which was developed to assess specific symptomatic adverse events directly from the patient. However, while the PROCTCAE is well positioned to capture specific drug side effects, its targeted nature may prevent comparisons tolerability across different drugs with varying toxicity profiles. To help address this issue, a global tolerability item would be useful. The Functional Assessment of Cancer Therapy‐General version (FACT‐G) includes a single item measure of patient‐reported bother from side effects of cancer therapy (“I am bothered by side effects of treatment”) rated on a five-point Likert scale. Likert scales are a commonly used psychometric technique in survey research. They are a widely used approach to scale responses in survey research. The term Likert scale is often used interchangeably with rating scale. In GP 5 the Likert scale ranges from 0 (Not at all) to 4 (Very Much). Previous research demonstrates that greater bother from cancer therapy side effects is associated with clinician‐reported adverse events and a greater likelihood of discontinuing treatment prior to completing protocol therapy. Greater bother from side effects has demonstrated an association with lower quality of life and less enjoyment of life, and is associated with early treatment discontinuation across multiple cancer trials.
Although initial research has indicated the possible utility of the FACIT GP5 item, additional research is required to determine whether it is suitable for use in clinical trials to capture tolerability. Particularly, investigation across certain cancer types, quantification of its relationship to dose and regimen options with common cancer drugs, and its association with broader outcomes like health-related quality of life.
This research will leverage existing trial data that covers a range of tumor types and anti-cancer therapies. This will provide information about the suitability of the FACIT GP5 item in a range of settings and contexts. We will focus on statistical methods such as correlation and regression to identify pre-specified associations.
Contribution
If this research demonstrates the suitability of the FACIT GP5 as a trial endpoint, future trials of new cancer therapies can then incorporate a single item summary of the patient experience of side effects. This information can be useful in treatment discussions and decision making, which is an essential consideration for patient care in oncology.
Requested Studies:
A Randomized, 3 Arm, Multicenter, Phase III Study to Evaluate the Efficacy and the Safety of T-DM1 Combined With Pertuzumab or T-DM1 Combined With Pertuzumab-Placebo (Blinded for Pertuzumab), Versus the Combination of Trastuzumab Plus Taxane, as First Line Treatment in HER2 Positive Progressive or Recurrent Locally Advanced or Metastatic Breast Cancer
Data Contributor: Roche
Study ID: NCT01120184
Sponsor ID: BO22589
Randomized, Open-Label, Phase 3 Study of Pemetrexed Plus Carboplatin and Bevacizumab Followed by Maintenance Pemetrexed and Bevacizumab Versus Paclitaxel Plus Carboplatin and Bevacizumab Followed by Maintenance Bevacizumab in Patients With Stage IIIB or IV Nonsquamous Non-Small Cell Lung Cancer
Data Contributor: Lilly
Study ID: NCT00762034
Sponsor ID: 9707
AXITINIB (AG-013736) AS SECOND LINE THERAPY FOR METASTATIC RENAL CELL CANCER: AXIS TRIAL
Data Contributor: Pfizer Inc.
Study ID: NCT00678392
Sponsor ID: A4061032
AG-013736 (AXITINIB) FOR THE TREATMENT OF METASTATIC RENAL CELL CANCER
Data Contributor: Pfizer Inc.
Study ID: NCT00920816
Sponsor ID: A4061051
A RANDOMIZED, MULTICENTER, DOUBLE-BLIND PHASE 3 STUDY OF PD-0332991 (ORAL CDK 4/6 INHIBITOR) PLUS LETROZOLE VERSUS PLACEBO PLUS LETROZOLE FOR THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH ER (+), HER2 (-) BREAST CANCER WHO HAVE NOT RECEIVED ANY PRIOR SYSTEMIC ANTI CANCER TREATMENT FOR ADVANCED DISEASE
Data Contributor: Pfizer Inc.
Study ID: NCT01740427
Sponsor ID: A5481008
A Phase III, Open-Label, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Bevacizumab Versus Sunitinib in Patients With Untreated Advanced Renal Cell Carcinoma
Data Contributor: Roche
Study ID: NCT02420821
Sponsor ID: WO29637
A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer
Data Contributor: Roche
Study ID: NCT00567190
Sponsor ID: TOC4129g