While the side effects of anthracycline and taxane based chemotherapy are well characterized, introduction of experimental agents and immunotherapy in the neoadjuvant and adjuvant setting may significantly alter the toxicity profiles of these regimens, resulting in short and long-term changes in patient quality of life (QOL).
I-SPY 2 is a phase 2 trial investigating novel targeted therapies and immunotherapy in combination with standard chemotherapy in the neoadjuvant setting for Mammaprint high-risk stage 2 and 3 breast cancers. A QOL sub-study was introduced into the I-SPY 2 trial platform in 2012. All patients who consent to screen for the I-SPY 2 trial receive a baseline QOL questionnaire. Patients who consent to the treatment phase of I-SPY 2 also complete questionnaires on the first day of treatment, mid-way through neoadjuvant treatment, prior to surgery, and then 1, 6, 12 and 24 months post-surgery. Instruments have included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) QLQ C30 and BR23, as well as NCI Patient- Reported Outcomes Measurement Information System (PROMIS) measures, the National Comprehensive Cancer Network (NCCN) Distress Thermometer, and a Fear of Recurrence (FOR) instrument. We are currently implementing an electronic platform for survey collection and modifying the survey instruments to incorporate 31 items from the Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system along with previously included PROMIS items in domains of physical, psychological, cognitive, and sexual function, the Distress Thermometer, and the FOR instrument. During neoadjuvant treatment, patients will also complete weekly abbreviated surveys containing PRO-CTCAE items only. We are using the data from these measures to generate a Clinical Benefit Index (CBI), a single composite score that integrates a PROMIS Preference (PROPr) score with a clinical efficacy assessment (residual cancer burden- RCB index) to provide new insight into the overall impact that therapeutic agents in ISPY2 have on cancer recurrence risk, general health, and QOL.
The primary objective of the QOL study is to evaluate the short- and long-term impact on QOL of novel agents added to standard treatment in high-risk breast cancer patients receiving neoadjuvant therapy. Factors including patient age, hormone receptor and HER2 status, and response to treatment by residual cancer burden will be evaluated to understand their impact on a patients’ QOL trajectory over time. A secondary objective is to compare patient reported toxicities (using PRO-CTCAE measures) with clinician-reported adverse events.
The I-SPY 2 trial has registered 2729 patients to date and there are 18 sites open across the US. Since the initiation of the QOL study, at least one QOL survey has been collected from 1066 patients. Given the adaptive design, enrollment for each agent varies based on patient outcomes, but collection of PRO measures on all patients will continue as new agents enter the trial. Clinical trial information: NCT01042379.