Abstract P4-11-08: Impact of treatment on quality of life (QOL) in the BEACON study, a randomized phase III trial of etirinotecan pegol (EP) versus treatment of physician's choice (TPC) in patients (pts) with advanced breast cancer (aBC) whose disease has progressed following anthracycline (A), taxane (T) and capecitabine (C)
Authors: Cortes J , Awada A , Perez EA , Rugo HS , Twelves C , Im S-A , Zhao C , Hoch U , Ney J , Hannah AL , O'Shaughnessy J 
Published: May 2016

Abstract
Background: The need remains for novel agents that prolong survival and/or improve QOL in women with aBC. EP is a long-acting topoisomerase 1 inhibitor engineered to produce sustained exposure to irinotecan and its active metabolite SN38. Given previous efficacy seen in an earlier phase II trial in MBC, EP 145 mg/m2 every 3 weeks was compared to TPC (one of 7 single-agent regimens) in the randomized phase 3 BEACON study (NCT01492101). As reported at ASCO 2015 (abstract 1001), EP prolonged median overall survival by 2.1 months, although this did not reach statistical significance (12.4 vs 10.3 months; HR 0.87, p=0.08). Grade ≥ 3 adverse events were significantly less common with EP (48% vs 63% with TPC, p&lt;0.001). We now present results of the QOL analyses.
Methods: Patients completed validated health-related QoL (HRQoL) questionnaires, EORTC QLQ-C30 (version 3.0) and breast cancer-specific QLQ-BR23, pretreatment and every 8 weeks until progression, death or withdrawal of consent. Questionnaires were scored according to the EORTC manual. For each scale, raw scores were standardized via a linear transformation to a range from 0 to 100. Absolute scores and changes from baseline were analyzed longitudinally and categorically using a 5-point difference calculated by treatment group. Comparisons between treatment groups were conducted to evaluate the differences in global health status, functional scores and symptoms over time.
Results: The majority of patients who were randomized (total: 733/852 [86%], EP: 378/429 [88%], TPC: 355/423 [84%]) completed at least one post-baseline HRQoL questionnaire. In the EORTC QLQ-C30, grade ≥ 3 AEs significantly impacted HRQoL measured by global health status and 5 additional functional domains. Of the six domains, compared to TPC in a longitudinal analysis, EP was statistically superior in the mean treatment effect through Week 32 in global health status p=0.02 and physical functioning scale p=0.01. EP was also numerically superior in all other scales. In EORTC QLQ-C30 and BR-23, a total of 13 symptoms were measured and categorically analyzed. There were no treatment differences in 7 of 13 symptom scales. EP was associated with worsening of 3 symptom scales: appetite loss, nausea/vomiting, and diarrhea. TPC was associated with worsening of 2 symptom scales: dyspnea and systemic side effects.
Conclusions: In the phase 3 BEACON trial comparing EP to TPC, the more favorable toxicity profile of EP resulted in an improvement in global health status and physical function (results of the symptom scales confirmed the different toxicities of the two arms). EP remains a promising investigational therapy for aBC.
Citation Format: Cortes J, Awada A, Perez EA, Rugo HS, Twelves C, Im S-A, Zhao C, Hoch U, Ney J, Hannah AL, O'Shaughnessy J. Impact of treatment on quality of life (QOL) in the BEACON study, a randomized phase III trial of etirinotecan pegol (EP) versus treatment of physician's choice (TPC) in patients (pts) with advanced breast cancer (aBC) whose disease has progressed following anthracycline (A), taxane (T) and capecitabine (C). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-11-08.