F Trillsch1, S Mahner2, F Hilpert3, L Davies4, E García-Martínez5, G Kristensen6, A Savarese7, P Vuylsteke8, M Los9, F Zagouri10, L Gladieff11, J Sehouli12, C Khoon Lee4, V Gebski4, E Pujade-Lauraine13. 1. 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. 2. Department of Gynecology and Obstetrics, AGO and University of Munich, Munich sven.mahner@med.uni-muenchen.de. 3. AGO and Onkologisches Therapiezentrum am Krankenhaus Jerusalem, Hamburg, Germany. 4. NHMRC Clinical Trials Centre, University of Sydney, Camperdown, Australia. 5. Department of Hematology and Medical Oncology, GEICO and University Hospital JM Morales Meseguer, Murcia, Spain. 6. 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. 7. Department of Medical Oncology '1', MITO and Regina Elena National Cancer Institute, Rome, Italy. 8. Medical Oncology, BGOG and CHU UCL Namur, Site Sainte Elisabeth, Namur, Belgium. 9. Department of Internal Medicine/Oncology, DGOG and St Antonius Ziekenhuis, Nieuwegein, The Netherlands. 10. Department of Clinical Therapeutics, HECOG and University of Athens, Medical School, Athens, Greece. 11. Institut Claudius-Regaud, Departement d'Oncologie Médicale, GINECO and Centre Hospitalier Universitaire de Toulouse, Toulouse, France. 12. Department of Gynecology, AGO and Charité Medical University of Berlin, Campus Virchow Klinikum, Berlin, Germany. 13. GINECO and Université Paris Descartes, AP-HP, Hôpitaux Universitaires Paris Centre, Site Hôtel Dieu, Oncologie, Paris, France.
Abstract
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.
RCT Entities:
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.