Prognostic and predictive effects of primary vs secondary platinum resistance for bevacizumab treatment for platinum-resistant ovarian cancer (AURELIA phase 111) Ovarian Cancer and Us OVARIAN CANCER and US Ovarian Cancer and Us

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Saturday, June 11, 2016

Prognostic and predictive effects of primary vs secondary platinum resistance for bevacizumab treatment for platinum-resistant ovarian cancer (AURELIA phase 111)



abstract
 June 10, 2016

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). 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 vs 5.6 months in PPR patients; P<0.001) and OS (median 22.2 vs 13.7 months, respectively; P<0.001) but not PROs (22% vs 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 endpoint in the chemotherapy-alone subgroup. The magnitude of PFS benefit from bevacizumab appeared greater in SPR than PPR patients (HR 0.30 vs 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 (secondary platinum resistance) than PPR (primary platinum resistance) patients with equally improved PROs (patient-reported outcomes). 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.

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