Prognostic and predictive effects of primary versus secondary platinum resistance for bevacizumab treatment for platinum-resistant ovarian cancer in the AURELIA trial.
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 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.



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).



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.
Department of Gynecology and Obstetrics, AGO and University of Munich, Munich Department of Gynecology and Gynecologic Oncology, AGO and University Medical Center Hamburg-Eppendorf, Hamburg.
F
F
Trillsch
Department of Gynecology and Obstetrics, AGO and University of Munich, Munich sven.mahner@med.uni-muenchen.de.
S
S
Mahner
AGO and Onkologisches Therapiezentrum am Krankenhaus Jerusalem, Hamburg, Germany.
F
F
Hilpert
NHMRC Clinical Trials Centre, University of Sydney, Camperdown, Australia.
L
L
Davies
Department of Hematology and Medical Oncology, GEICO and University Hospital JM Morales Meseguer, Murcia, Spain.
E
E
García-Martínez
Department of Gynecologic Oncology and Institute for Cancer Genetics and Informatics and Institute for Clinical Medicine, NSGO and Oslo University Hospital, University of Oslo, Oslo, Norway.
G
G
Kristensen
Department of Medical Oncology '1', MITO and Regina Elena National Cancer Institute, Rome, Italy.
A
A
Savarese
Medical Oncology, BGOG and CHU UCL Namur, Site Sainte Elisabeth, Namur, Belgium.
P
P
Vuylsteke
Department of Internal Medicine/Oncology, DGOG and St Antonius Ziekenhuis, Nieuwegein, The Netherlands.
M
M
Los
Department of Clinical Therapeutics, HECOG and University of Athens, Medical School, Athens, Greece.
F
F
Zagouri
Institut Claudius-Regaud, Departement d'Oncologie Médicale, GINECO and Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
L
L
Gladieff
Department of Gynecology, AGO and Charité Medical University of Berlin, Campus Virchow Klinikum, Berlin, Germany.
J
J
Sehouli
NHMRC Clinical Trials Centre, University of Sydney, Camperdown, Australia.
C
C
Khoon Lee
NHMRC Clinical Trials Centre, University of Sydney, Camperdown, Australia.
V
V
Gebski
GINECO and Université Paris Descartes, AP-HP, Hôpitaux Universitaires Paris Centre, Site Hôtel Dieu, Oncologie, Paris, France.
E
E
Pujade-Lauraine
D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D010984:Platinum / Q000008:administration & dosage* / Q000009:adverse effects; D011379:Prognosis; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D010984:Platinum; D017239:Paclitaxel
anti-angiogenic therapy; bevacizumab; platinum resistance; prognostic factors; recurrent ovarian cancer; response rates