The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer , neoadjuvant chemotherapy and interval cytoreduction are non-inferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality .
PURPOSE To provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer .
Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial
Summary Background The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to st and ard chemotherapy , with the greatest effect in patients at high risk of disease progression . We report the final overall survival results of the trial . Methods ICON7 was an international , phase 3 , open-label , r and omised trial undertaken at 263 centres in 11 countries across Europe , Canada , Australia and New Zeal and . Eligible adult women with newly diagnosed ovarian cancer that was either high-risk early-stage disease ( International Federation of Gynecology and Obstetrics [ FIGO ] stage I – IIa , grade 3 or clear cell histology ) or more advanced disease ( FIGO stage IIb – IV ) , with an Eastern Cooperative Oncology Group performance status of 0–2 , were enrolled and r and omly assigned in a 1:1 ratio to st and ard chemotherapy ( six 3-weekly cycles of intravenous carboplatin [ AUC 5 or 6 ] and paclitaxel 175 mg/m2 of body surface area ) or the same chemotherapy regimen plus bevacizumab 7·5 mg per kg bodyweight intravenously every 3 weeks , given concurrently and continued with up to 12 further 3-weekly cycles of maintenance therapy . R and omisation was done by a minimisation algorithm stratified by FIGO stage , residual disease , interval between surgery and chemotherapy , and Gynecologic Cancer InterGroup group . The primary endpoint was progression-free survival ; the study was also powered to detect a difference in overall survival . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N91273375 . Findings Between Dec 18 , 2006 , and Feb 16 , 2009 , 1528 women were enrolled and r and omly assigned to receive chemotherapy ( n=764 ) or chemotherapy plus bevacizumab ( n=764 ) . Median follow-up at the end of the trial on March 31 , 2013 , was 48·9 months ( IQR 26·6–56·2 ) , at which point 714 patients had died ( 352 in the chemotherapy group and 362 in the bevacizumab group ) . Our results showed evidence of non-proportional hazards , so we used the difference in restricted mean survival time as the primary estimate of effect . No overall survival benefit of bevacizumab was recorded ( restricted mean survival time 44·6 months [ 95 % CI 43·2–45·9 ] in the st and ard chemotherapy group vs 45·5 months [ 44·2–46·7 ] in the bevacizumab group ; log-rank p=0·85 ) . In an exploratory analysis of a predefined subgroup of 502 patients with poor prognosis disease , 332 ( 66 % ) died ( 174 in the st and ard chemotherapy group and 158 in the bevacizumab group ) , and a significant difference in overall survival was noted between women who received bevacizumab plus chemotherapy and those who received chemotherapy alone ( restricted mean survival time 34·5 months [ 95 % CI 32·0–37·0 ] with st and ard chemotherapy vs 39·3 months [ 37·0–41·7 ] with bevacizumab ; log-rank p=0·03 ) . However , in non-high-risk patients , the restricted mean survival time did not differ significantly between the two treatment groups ( 49·7 months [ 95 % CI 48·3–51·1 ] ) in the st and ard chemotherapy group vs 48·4 months [ 47·0–49·9 ] in the bevacizumab group ; p=0·20 ) . An up date d analysis of progression-free survival showed no difference between treatment groups . During extended follow-up , one further treatment-related grade 3 event ( gastrointestinal fistula in a bevacizumab-treated patient ) , three grade 2 treatment-related events ( cardiac failure , sarcoidosis , and foot fracture , all in bevacizumab-treated patients ) , and one grade 1 treatment-related event ( vaginal haemorrhage , in a patient treated with st and ard chemotherapy ) were reported . Interpretation Bevacizumab , added to platinum-based chemotherapy , did not increase overall survival in the study population as a whole . However , an overall survival benefit was recorded in poor-prognosis patients , which is concordant with the progression-free survival results from ICON7 and GOG-218 , and provides further evidence towards the optimum use of bevacizumab in the treatment of ovarian cancer . Funding The National Institute for Health Research through the UK National Cancer Research Network , the Medical Research Council , and Roche
The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer , neoadjuvant chemotherapy and interval cytoreduction are non-inferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality .
PURPOSE To provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer .