Patient‐reported outcomes enhance understanding of the impact of pazopanib in soft tissue sarcoma

Little research has explored quality of life in patients with advanced soft tissue sarcoma. The report by Coens and colleagues in this issue of Cancer advances understanding of how 1 targeted therapy—pazopanib—affects well being in this group. The analyses reported in their article investigate health-related quality of life (HRQoL) as an outcome in Pazopanib for Metastatic Soft-Tissue Sarcoma (PALETTE), a randomized clinical trial (RCT) that compared pazopanib, an orally administered, multitarget tyrosine kinase inhibitor, with placebo in 369 patients who had failed at least 1 previous chemotherapy regimen. The PALETTE trial demonstrated a significant benefit in progression-free survival (PFS) for the pazopanib arm, with a time to progression of 4.6 months compared with 1.6 months in the placebo arm. However, more toxicity was associated with pazopanib, including significantly higher fatigue, diarrhea, nausea, weight loss, and hypertension. The current report provides additional information regarding patient perspectives regarding the impact of pazopanib on their lives. The study team used a well established questionnaire, the 30-item core European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), to assess HRQoL at baseline and at 3month follow-up assessments. The primary HRQoL outcome was global health status (GHS). In this questionnaire, GHS is measured by 2 items that ask patients to rate their “overall quality of life” and “overall health” during the past week on 7-point scales from 1 (very poor) to 7 (excellent). The EORTC QLQ-C30 also includes items assessing functioning and symptom experience. The results indicated that GHS did not differ between the pazopanib and placebo arms, although the patient-reported symptom experience echoed the toxicity data: statistically and clinically significant higher fatigue, diarrhea, nausea/vomiting, and appetite loss in patients receiving pazopanib. Although their original hypothesis was that pazopanib would result in improved GHS, the authors conclude that a lack of GHS deterioration in the face of considerable symptomatology supports the HRQoL benefits of this agent. There are many strengths of this study. These include the specification of an a priori hypothesis, the use of validated assessment tools and analytic strategies, and adherence to the Consolidated Standards of Reporting Trials PatientReported Outcome (CONSORT-PRO) extension guidelines for reporting. Missing data are often a concern in HRQoL research, particularly in studies of advanced disease. In this study, HRQoL questionnaire completion rates were excellent, with greater than 75% of eligible patients completing surveys at all 4 time points. In addition, the authors conducted thorough analyses of the potential impact of missing data and noted that their conclusions were unchanged. They also investigated HRQoL as a prognostic variable and, consistent with considerable previous research, observed that HRQoL was a significant predictor of length of survival but was not predictive of response to treatment. The primary conclusion of this study—that increased PFS was associated with more symptoms, but not with compromised HRQoL—has important implications. Some agencies, such as the US Food and Drug Administration, have offered specific guidance suggesting that well defined symptoms reflecting differences among therapies are the most appropriate indicators to demonstrate patient impact and that broader, less specific measures like quality of life are not the preferred approaches to evaluating drug indications and labeling. It should be noted that not all agencies have the same perspective on this issue: organizations like the European Medicines Agency are more likely to approve agents based on higher order constructs, such as quality of life. The study by Coens et al provides support for why measuring overall HRQoL is important as well as how patient perspectives provide significant contributions to clinical trials. If only