© 2013 Elsevier Ltd. All rights reserved.
Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the International Collaboration on Ovarian Neoplasms (ICON7) phase 3 randomised trial
aLeeds Institute of Molecular Medicine, University of Leeds, St James's Institute of Oncology, Leeds, UK
bMedical Research Council Clinical Trials Unit, London, UK
cUniversité Paris Descartes, AP-HP, Hôpitaux Universitaires Paris Centre, Hôtel-Dieu, Paris, France
dDepartment of Gynecologic Oncology and Institute of Medical Informatics, Oslo University Hospital, Oslo, Norway
eDepartment of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada
fAustralia New Zealand Gynaecological Oncology Group, University of Sydney, Camperdown, NSW, Australia
gNational Health and Medical Research Council Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia
hDepartment of Gynecology and Obstetrics, University of Schleswig-Holstein, Kiel, Germany
iDepartment of Hematology and Medical Oncology, Institute of Health Research Hospital Clinico, University of Valencia, Valencia, Spain
jDepartment of Women's Cancer, Institute for Women's Health, University College London, London, UK
kF Hoffmann-La Roche, Basel, Switzerland
lStädtisches Klinikum Solingen, Klinik für Gynäkologie und Geburtshilfe, Solingen, Germany
mDepartment of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada
nCambridge Cancer Trials Centre, Cambridge, UK
oPrincess Margaret Hospital, Toronto, ON, Canada
pSt James's Institute of Oncology, St James's University Hospital, Leeds, UK
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All 1528 women (764 in both the standard chemotherapy and the bevacizumab groups) enrolled in ICON7 were asked to provide data on QoL. shows concordance with data collection by group. At baseline, 684 (90%) women in the standard chemotherapy group and 691 (90%) in the bevacizumab group provided complete data. By 54 weeks, 388 (51%) women in the standard chemotherapy group and 502 (66%) in the bevacizumab group had provided data; 254 (33%) women who received standard chemotherapy and 147 (19%) in the bevacizumab group had either progressive disease or had died (so no QoL data were sought), with an imbalance between the two groups (), and QoL data were missing for 122 (16%) women in the standard group and 115 (15%) of those in the bevacizumab group. Specific reasons for these missing data forms were given for 101 women (6·6%; 50 [6·5%] in the standard chemotherapy group and 51 [6·7%] in the bevacizumab group). For 85 of 101 forms (44 in the standard chemotherapy group and 41 in the bevacizumab group) the reason was centre administrative oversight, but for 15 (six in the standard chemotherapy group and nine in the bevacizumab group) it was because of either a patient declining to complete the form or illness. One patient in the bevacizumab group did not complete a data form because they were on holiday.
Attrition in returns of health-related quality-of-life data
During the 18-week period of chemotherapy treatment in both groups, mean global QoL for women with data from both baseline and week 18 (333 women in the standard chemotherapy group and 444 women in the bevacizumab group) improved by 7·2 points (SD 24·4). A difference between the group mean global QoL scores of 5·1 points (95% CI 2·9–7·4) was noted at the end of chemotherapy when analysed for all women with available data (). The primary outcome, mean global QoL at 54 weeks, was better for women in the standard chemotherapy group (76·1 points [SD 18·2]) than for those in the bevacizumab group (69·7 points [19·1]). This difference, 6·4 points (95% CI 3·7–9·0), is clinically small by modern criteria18
but statistically significant (p<0·0001 by ANOVA). The number of women whose global QoL score improved by at least 10 points between baseline and 54 weeks was 221 of 333 (66%) with standard chemotherapy and 250 of 444 (56%) with bevacizumab (odds ratio 0·58, 95% CI 0·42–0·80; p=0·001). This finding was also significant when all available data during the 54-week period were included and mean individual area under the global QoL–time curves were compared between groups, controlled for baseline score (p<0·0001, ANOVA).
Mean global quality-of-life score between groups at key timepoints for all patients with available data
Analysis of our a-priori hypotheses did not support a difference between groups during the chemotherapy course in gastrointestinal problems or problems related to the surgical scar (). In the continuation bevacizumab phase, we did not note a difference between groups in the trajectory of social functioning or fatigue ().
Analyses of three quality-of-life hypotheses
shows data from the exploratory analysis of other subscales in the C30 and OV28 instruments. All differences were in favour of the standard chemotherapy group. Bevacizumab was associated with clinically small but statistically significant decrements of role functioning, financial worries, attitudes to disease or treatment, hormonal symptoms, and rash (all p<0·01).
Exploratory analyses of quality-of-life subscales
After imputation of global QoL of 0 for patients who had died, we imputed a range of mean global QoL decrements (as estimates of the effect of progressive disease upon global QoL). Imputing a decrement of at least a 20-point reduction in global QoL for the effect of relapse of the cancer did not alter our findings of a statistically significant, clinically small, deficit in QoL for the bevacizumab group (). If the decrement in global QoL from disease progression is imputed as a 30–50-point reduction then there is no statistically significant difference between the groups. If the decrement is imputed as a 60–70-point reduction, then the analyses favour the bevacizumab group. A clinically plausible estimate of global QoL in relapsed ovarian cancer was made from the ICON4 trial (unpublished, Medical Research Council Clinical Trials Unit, London, UK). The mean global QoL (using the C30) for women being treated for ovarian cancer at first relapse in ICON4 was 61 points compared with a baseline global QoL in ICON7 of 57 points.