Emerging Role for Bevacizumab in Combination With Chemotherapy for Patients With Platinum-Resistant Ovarian Cancer
Authors: Joyce F. Liu, Stephen A. Cannistra
Journal: Journal of Clinical Oncology (2014)

each of these three studies, AURELIA observed a statistically significant benefit in progression-free survival (PFS) with the addition of bevacizumab to chemotherapy, with an absolute 3.3-month improvement in median PFS from 3.4 months in the chemotherapy-alone arm to 6.7 months in the chemotherapy plus bevacizumab arm (hazard ratio, 0.48; 95% CI 0.38 to 0.60; P , .001). This margin of benefit is similar to those reported in the GOG 218, ICON7, and OCEANS studies, which suggests a remarkable consistency in the observed effects of combining bevacizumab with chemotherapy in several different settings in ovarian cancer. However, as with the other randomized phase III studies, no overall survival (OS) benefit was observed in the chemotherapy plus bevacizumab arm in AURELIA. Similar to the OCEANS trial, the combination of bevacizumab and chemotherapy in AURELIA also significantly improved the overall response rate (ORR) from 11.8% to 27.3% ( P 5 .001), as assessed by RECIST criteria. No new safety signals were observed in the chemotherapy plus bevacizumab arm, with the incidence of $ grade 2 hypertension and proteinuria being similar to that of other studies. The incidence of $ grade 2 GI perforation was 2.2% in the chemotherapy plus bevacizumab arm compared with 0% in the chemotherapy-alone arm; again, this is consistent with the findings of other studies. Interestingly, the incidence of hand-foot syndrome and peripheral sensory neuropathy was greater in the chemotherapy plus bevacizumab arm compared with chemotherapy alone, which most likely relates to the longer duration of time that patients received either PLD or paclitaxel in the combination arm (because patients remained on chemotherapy for a longer period of time without disease progression). The incidence of treatment-related death was 2.8% in each arm. Importantly, AURELIA also studied PROs as a separate preplanned end point and found that more patients in the chemotherapy plus bevacizumab arm achieved a $ 15% improvement in abdominal/GI symptom PROs (as assessed by the Quality of Life Questionnaire–OV28 abdominal/GI symptom subscale) at week 8 or 9 (21.9% v 9.3%; P 5 .002). 4 This may represent an underestimate of the PRO improvement with chemotherapy plus bevacizumab, given that only 65% of patients in this trial had sufficient symptoms at baseline for a difference to be detectable. It is noteworthy that AURELIA is the first study incorporating bevacizumab in ovarian cancer to report an improvement in PROs. In the setting of platinum-resistant ovarian cancer, in which therapy is palliative, improvement in PROs is of potential importance even in the absence of an OS benefit. In contrast, in the studies incorporating bevacizumab into first-line and subsequent maintenance treatment, GOG 218 did not demonstrate an improvement in PROs, and ICON7 demonstrated a slight worsening in PROs. 8,9 Perhaps it is not surprising that PROs were not improved and were possibly compromised by introducing bevacizumab into the first-line setting, where most patients experience relatively few disease-related symptoms once chemotherapy begins, and when the magnitude of median PFS prolongation with bevacizumab is modest. In the relapsed setting, OCEANS did not include a PRO end point. 7 Although the results reported in these studies add to our experience with bevacizumab in ovarian cancer, interpreting the data from these reports is not straightforward. AURELIA differs from GOG 218 and OCEANS in that it is an open-label study without a placebo