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The measurement of treatment-related adverse event (AE) outcomes in clinical trials can often be limited to clinician reporting. But clinical practice is evolving to include more patient-reported outcome (PRO) measures, according to the investigators of a newly published study looking at patient-reported AEs and early discontinuation in patients with multiple myeloma (MM).¹ The Functional Assessment of Chronic Illness Therapy (FACIT) Measurement system is a patient self-report questionnaire that began decades ago as a cancer-specific measure of health-related quality of life (HRQOL) in breast, lung, and colon cancer, but now includes myriad cancer sites and has been adapted for measuring HRQOL in patients with many other chronic conditions, those with specific symptoms of disease, those with treatment-related AEs, and for measuring general patient-centered outcomes.²

Peipert and colleagues point to the FDA鈥檚 identification of overall AE impact and symptomatic AEs as two PRO concepts directly associated with treatment tolerability. A commonly used source of PROs in cancer trials is the Functional Assessment of Cancer Therapy (FACT) measurement system, which includes the overall HRQoL core score, or FACT鈥揋eneral (FACT-G). Many tumor-specific assessments鈥攕uch as in breast and colon cancers鈥攗se FACT-G. A general physical well-being scale known as the FACT-G Physical Well-Being scale鈥攐r GP5鈥攁sks patients to rate on a 5-point scale (0=not at all; 5 = very much) the statement 鈥淚 am bothered by side effects of treatment.鈥� 

The current randomized, prospective survey study looked at the association between GP5 (administered at baseline and 1 month, 2.8 months, and 5.5 months after treatment initiation) and AE-related early treatment discontinuation (ETD) in 1,058 US-based patients (mean age = 64 years; 50.2% receiving VrD; 49.8% receiving KRd) newly diagnosed with MM prescribed bortezomib (VRd) or carfilzomib (KRd) plus lenalidomide and dexamethasone as induction therapy. 

At each assessment, the response options to the GP5 question, (鈥淚 am bothered by side effects of treatment,鈥�) were categorized as high AE bother (鈥渧ery much,鈥� 鈥渜uite a bit鈥�) or low AE bother (鈥渟omewhat,鈥� 鈥渁 little bit,鈥� and 鈥渘ot at all鈥�). The main study outcome was ETD due to AE (yes vs no) and logistic regression analysis was used to adjust for treatment group, performance status, gender, race, and disease stage. Worsening symptoms were categorized by whether they increased by 1 response category or 2 or more categories.

The investigators found that AE-related ETD occurred in 13.4% (n = 142) of patients. The adjusted odds ratio (aOR) of ETD for those with high AE bother by GP5 on therapy at 1 month, 2.8 months, and 5.5 months, respectively, was 2.20 (95%CI, 1.25-3.89), 3.41 (95%CI, 2.01-5.80), and 4.66 (95%CI, 1.69-12.83). For those experiencing a worsening of symptoms by 2 or more response categories on the GP5, the aOR of ETD at 2.8 months was 3.02 (95%CI, 1.64-5.54) and at 5.5 months the aOR was 5.49 (95%CI, 1.45-20.76).

The study鈥檚 lead investigator, Devin Peipert, PhD, assistant professor at Northwestern University Feinberg School of Medicine, Chicago, IL, believes this study is instructive for quickly identifying a patient-centered assessment of treatment side effects. 鈥淭his study shows that a patient's overall experience of side effects, potentially reflecting the impact of multiple toxicities, is a good predictor of whether or not they will drop out of a trial for adverse events. [Our] research demonstrates a brief way to determine if patients find their treatment intolerable, which in turn may be leveraged to optimize patient care.鈥�

鈥淎s we move toward trials that compare tolerability from the patient's perspective, we should consider endpoints that reflect overall side effect impact in addition to those capturing specific side effects,鈥� says Peipert. 鈥淎dditional research should examine how best to use patient reported outcomes鈥︹�� 

Published: May 15, 2024