TY - JOUR
TI - Prognostic and predictive effects of primary versus secondary platinum resistance for bevacizumab treatment for platinum-resistant ovarian cancer in the AURELIA trial
AU - Trillsch, F.
AU - Mahner, S.
AU - Hilpert, F.
AU - Davies, L.
AU - García-Martínez, E.
AU - Kristensen, G.
AU - Savarese, A.
AU - Vuylsteke, P.
AU - Los, M.
AU - Zagouri, F.
AU - Gladieff, L.
AU - Sehouli, J.
AU - Khoon Lee, C.
AU - Gebski, V.
AU - Pujade-Lauraine, E.
JO - Annals of Oncology
PY - 2016
VL - 27
TODO - 9
SP - 1733-1739
PB - Oxford University Press
SN - 0923-7534, 1569-8041
TODO - 10.1093/annonc/mdw236
TODO - bevacizumab;  doxorubicin;  paclitaxel;  topotecan;  antineoplastic agent;  bevacizumab;  monoclonal antibody;  paclitaxel;  platinum;  platinum complex, adult;  aged;  Article;  breast cancer;  cancer prognosis;  controlled study;  drug efficacy;  drug safety;  human;  intention to treat analysis;  major clinical study;  median survival time;  ovary cancer;  overall survival;  phase 3 clinical trial;  priority journal;  progression free survival;  randomized controlled trial;  risk benefit analysis;  treatment response;  disease free survival;  drug effects;  drug resistance;  female;  middle aged;  ovary tumor;  pathology;  prognosis;  treatment outcome, Aged;  Antibodies, Monoclonal, Humanized;  Antineoplastic Combined Chemotherapy Protocols;  Bevacizumab;  Disease-Free Survival;  Drug Resistance, Neoplasm;  Female;  Humans;  Middle Aged;  Organoplatinum Compounds;  Ovarian Neoplasms;  Paclitaxel;  Platinum;  Prognosis;  Treatment Outcome
TODO - Background: Progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes (PROs) were significantly improved by adding bevacizumab to chemotherapy for platinum-resistant ovarian cancer (PROC) in the phase III AURELIA trial. We explored treatment outcomes according to primary platinum resistance (PPR) versus secondary platinum resistance (SPR). Patients and methods: Patients were categorized as PPR (disease progression <6 months after completing first-line platinum therapy) or SPR (progression ≥6 months after first platinum but <6 months after second). The exploratory Cox and logistic regression analyses correlated PFS, ORR, overall survival (OS), and PROs with the time to development of platinum resistance. Results: Baseline characteristics were similar in patients with PPR (n = 262; 73%) and SPR (n = 99; 27%), although ascites were more common in the PPR subgroup. In bevacizumab-treated patients (n = 179), SPR was associated with improved PFS (median 10.2 versus 5.6 months in PPR patients; P < 0.001) and OS (median 22.2 versus 13.7 months, respectively; P < 0.001) but not PROs (22% versus 22% with improved abdominal/gastrointestinal symptoms at week 8/9). In multivariate analyses, SPR remained an independent prognostic factor for better PFS [adjusted hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.25-0.67; P < 0.001] and OS (HR 0.49, 95% CI 0.30-0.80; P = 0.005) in bevacizumab-treated patients, but was not statistically significant for either end point in the chemotherapy-alone subgroup. The magnitude of PFS benefit from bevacizumab appeared greater in SPR than PPR patients (HR 0.30 versus 0.55, respectively; interaction P = 0.07) with a similar direction of effect for OS (interaction P = 0.18). Conclusions: In bevacizumab-treated patients, PFS and OS were more favorable in SPR than PPR patients with equally improved PROs. The PFS and OS benefit from combining bevacizumab with chemotherapy was more pronounced in SPR than PPR PROC. PPR versus SPR should be a stratification factor in future trials evaluating anti-angiogenic therapy for PROC. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
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