Patient-reported outcome results from the open-label phase III AURELIA trial evaluating bevacizumab-containing therapy for platinum-resistant ovarian cancer

Abstract

Purpose: To determine the effects of bevacizumab on patient-reported outcomes (PROs; secondary end point) in the AURELIA trial.

Patients and methods: Patients with platinum-resistant ovarian cancer were randomly assigned to chemotherapy alone (CT) or with bevacizumab (BEV-CT). PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Ovarian Cancer Module 28 (EORTC QLQ-OV28) and Functional Assessment of Cancer Therapy-Ovarian Cancer symptom index (FOSI) at baseline and every two or three cycles (8/9 weeks) until disease progression. The primary PRO hypothesis was that more patients receiving BEV-CT than CT would achieve at least a 15% (≥ 15-point) absolute improvement on the QLQ-OV28 abdominal/GI symptom subscale (items 31-36) at week 8/9. Patients with missing week 8/9 questionnaires were included as unimproved. Questionnaires from all assessments until disease progression were analyzed using mixed-model repeated-measures (MMRM) analysis. Sensitivity analyses were used to determine the effects of differing assumptions and methods for missing data.

Results: Baseline questionnaires were available from 89% of 361 randomly assigned patients. More BEV-CT than CT patients achieved a ≥ 15% improvement in abdominal/GI symptoms at week 8/9 (primary PRO end point, 21.9% v 9.3%; difference, 12.7%; 95% CI, 4.4 to 20.9; P = .002). MMRM analysis covering all time points also favored BEV-CT (difference, 6.4 points; 95% CI, 1.3 to 11.6; P = .015). More BEV-CT than CT patients achieved ≥ 15% improvement in FOSI at week 8/9 (12.2% v 3.1%; difference, 9.0%; 95% CI, 2.9% to 15.2%; P = .003). Sensitivity analyses gave similar results and conclusions.

Conclusion: Bevacizumab increased the proportion of patients achieving a 15% improvement in patient-reported abdominal/GI symptoms during chemotherapy for platinum-resistant ovarian cancer.

Trial registration: ClinicalTrials.gov NCT00976911.

Fig 1.

CONSORT diagram. BEV-CT, chemotherapy with bevacizumab; CT, chemotherapy; PRO, patient-reported outcome; PD, progressive disease.

Fig 2.

Compliance for the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire–Ovarian Cancer Module 28 (QLQ-OV28), Functional Assessment of Cancer Therapy–Ovarian Cancer Symptom Index (FOSI), and EORTC QLQ Cancer Module 30 (C30) questionnaires. (A) Baseline; (B) week 8/9; (C) week 16/18. (*) Denominator (patients known to be progression free) excludes patients whose disease progressed or who died or were lost to follow-up at least 14 days before the scheduled assessment date. BEV, bevacizumab; CT, chemotherapy.

Fig 3.

Primary and sensitivity analyses of the primary hypothesis (≥ 15% improvement in abdominal/GI symptoms [European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Ovarian Cancer Module 28]). 95% Pearson-Clopper CIs with the Hauck-Anderson continuity correction for the difference between arms. (*) 15% cutoff, items 31 to 36, missing questionnaires counted as no improvement. (†) 15% cutoff, items 31 to 37, missing questionnaires counted as no improvement. (‡) 10% cutoff, items 31 to 36, missing questionnaires counted as no improvement. (§) 15% cutoff, items 31 to 36, questionnaires missing for reasons other than disease progression (PD) were not included in denominator. (‖) 15% cutoff, items 31 to 36, all missing questionnaires excluded from denominator. BEV, bevacizumab; CT, chemotherapy.

Fig 4.

Mixed-model repeated-measures analyses for the abdominal/GI subscale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Ovarian Cancer Module. Estimates for the between-treatment group comparisons for each time point and for the entire profile were obtained. The estimates are presented with the corresponding 95% CIs in parentheses. BEV, bevacizumab; CT, chemotherapy.

Fig 5.

Mixed-model repeated-measures analysis for the Functional Assessment of Cancer Therapy–Ovarian Cancer Symptom Index. Estimates for the between-treatment group comparison for each time point and for the entire profile were obtained. The estimates are presented with the corresponding 95% CIs in parentheses. BEV, bevacizumab; CT, chemotherapy.

Fig 6.

Comparison of proportions of patients achieving improvement from baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Cancer Module (week 8/9). (A) Proportions were calculated including all patients with baseline questionnaires and counting those missing questionnaires at a subsequent time point as unimproved. (B) Patients with missing questionnaires after baseline were not included in the denominator. BEV, bevacizumab; CT, chemotherapy; QoL, quality of life.

Fig A1.

Cumulative distribution function plot of change from baseline in abdominal/GI symptoms (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Ovarian Cancer Module) at week 8/9 (intent-to-treat population). BEV, bevacizumab; CT, chemotherapy.