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

Trillsch, F.; Mahner, S.; Hilpert, F.; Davies, L.; García-Martínez, E.; Kristensen, G.; Savarese, A.; Vuylsteke, P.; Los, M.; Zagouri, F.; Gladieff, L.; Sehouli, J.; Lee, C. Khoon; Gebski, V. und Pujade-Lauraine, E. (2016): Prognostic and predictive effects of primary versus secondary platinum resistance for bevacizumab treatment for platinum-resistant ovarian cancer in the AURELIA trial. In: Annals of Oncology, Bd. 27, Nr. 9: S. 1733-1739

Abstract

Exploratory analyses of time to platinum resistance suggest better prognosis in bevacizumab-treated patients with secondary versus primary platinum resistance. Progression-free and overall survival benefit from bevacizumab was enhanced in secondary-resistant disease. Our findings should be considered when selecting stratification factors in future trials of anti-angiogenic therapy in this setting.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 a parts per thousand yen6 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0923-7534
• Sprache: Englisch