LAUSR

In the article that accompanies this editorial, Berry et al report quality-adjusted survival outcomes from a randomized, placebo-controlled phase 2 trial (REGOSARC) for patients with doxorubicin-pretreated soft-tissue sarcoma (STS). The researchers applied the quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) method to provide an integrated measure of clinical benefit. In nonadipocytic sarcoma patients, regorafenib was associated with a statistically significant improvement in progression-free survival (PFS; 4.0 vs 1.0 month with a placebo) and with a nonsignificant trend for overall survival (OS; 13.4 vs 9.0 months with a placebo). The time without symptoms of disease or grade 3 or 4 toxicity (TWiST) due to treatment was 4.8 and 2.0 months for the regorafenib and placebo arms, respectively. The time with a grade 3 or 4 toxicity (TOX) was 1.1 months for the regorafenib arm and 0.2 months for the placebo arm. The Q-TWiSTs were 8.0 and 5.7 months, respectively, and this indicated a 2.3-month Q-TWiST gain. The authors concluded that regorafenib offers improved clinical and quality-of-life outcomes for patients with advanced STS. This study makes important contributions to the growing literature demonstrating the value of comprehensive benefit-versus-risk assessments. Although the number of effective treatment options available to patients with advanced STS has increased, these treatments are limited by acute and chronic toxicities, thus limiting the benefit of these agents. Consequently, the selection of treatments for patients with STS is frequently guided by safety considerations and convenience. Therefore, it is important to assess treatment effectiveness both in terms of objective outcomes (eg, PFS or OS) and in terms of subjective patient-reported outcomes (PROs). PROs are any reports coming directly from a patient about how he or she feels and functions without interpretation of the patient’s response by a clinician or other health care professional. They include a range of outcomes, such as quality of life, symptoms, functional status, and well-being. Studies assessing PROs in patients with advanced STS are sparse, particularly in the metastatic setting. A recent study showed that patients with locally advanced, “inoperable”/metastatic STS have a significant symptom burden, including pain and dyspnea, that could negatively affect their quality of life. An assessment of PROs is critical for increasing patient centeredness in clinical trials, comparative effectiveness research, and cost-effectiveness research; PROs are increasingly considered a standard approach for evaluating quality of care. PRO measures have the potential to provide quality assessments that are meaningful and useful to patients and other stakeholders making health care decisions contingent on differential health care levels. For patients with advanced cancer, the 2 most important questions when a treatment is being considered are as follows: How much longer will I live if I take the treatment, and how will the treatment affect my quality of life? Clinical endpoints such as the PFS or response rate alone may not be meaningful to patients in the absence of information about associated toxicities or additional evidence of symptom palliation. The Q-TWiST methodology, developed by Goldhirsch et al, integrates both quality and quantity of life; it evaluates the tradeoff between toxicity and survival. Q-TWiST incorporates progression, survival, treatment toxicities, and utility measures into a single metric providing an integrated measure of clinical benefit. The survival is partitioned into 3 different health states: