Western Regional Blog – BC, YK, AB, NWT and Nunavut
PRIME Oncology, October 2013 issue
Three reports at ECC presented data defining the survival benefit of antiangiogenic agents in subgroups of patients with advanced ovarian cancer. Two studies (ICON7 and AURELIA) in their updated analyses investigated whether adding bevacizumab to chemotherapy in patients with either newly diagnosed or relapsed, platinum-resistant ovarian cancer improved OS. The third study (ICON6) investigated the benefit of cediranib, a potent oral inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, and VEGFR-3, in patients with relapsed, platinum-sensitive ovarian cancer. Together, these abstracts highlight the important role of antiangiogenic therapy in advanced ovarian cancer.
ICON7: Bevacizumab Extends Survival in High-Risk Subgroup
The final results of ICON7, which investigated the combination of bevacizumab (7.5 mg/kg) and standard carboplatin/paclitaxel chemotherapy in patients with newly diagnosed advanced ovarian cancer, failed to show an OS benefit in the primary intent-to-treat population (N = 1528), but showed a statistically significant and clinically meaningful OS benefit with bevacizumab in the predefined high-risk subgroup (N = 502 [33%]); suboptimally debulked stage III, stage IV, and nonoperated patients). In this subgroup, analysis by restricted means (preferred method because of the nonproportionality) showed 4.8-months improvement in OS (P = .007; 39.3 months for the bevacizumab arm vs 34.5 months for chemotherapy alone) and conventional log rank analysis showed 9.4 months improvement of OS for the bevacizumab arm (39.7 months for the bevacizumab arm vs 30.3 months for chemotherapy alone; HR = 0.78; P = .03). Amit Oza, MD (Princess Margaret Cancer Centre, Toronto, Canada), pointed out that OS difference in the high-risk subgroup is clinically meaningful. Rebecca Kristeleit, MD (London Bridge Hospital, London, United Kingdom), discussant of the abstract, highlighted that these results are practice changing and that first-line bevacizumab and 3-weekly chemotherapy should be considered standard of care for high-risk ovarian cancer.
Eur J Cancer. 2013;49(Suppl 3): Abstract LBA6.
AURELIA: The Bevacizumab OS Effect Observed in Weekly Paclitaxel Cohort
The AURELIA trial, which investigated the addition of bevacizumab to standard second-line chemotherapy in patients with relapsed, platinum-resistant ovarian cancer, demonstrated a significant 3-month improvement of PFS (primary endpoint), but failed to show a statistically significant OS benefit in the ITT population. However, an exploratory subgroup analysis identified a cohort of patients treated with weekly paclitaxel who appear to gain survival benefit with the addition of bevacizumab. In this subgroup (n = 115), median OS was 22.4 months in patients receiving paclitaxel (80 mg/m2 days 1, 8, 15, and 22 every 4 weeks) plus bevacizumab compared to 13.2 months with paclitaxel alone (HR = 0.65). Dr 22
Kristeleit addressed several limitations of this study, including lack of power to show statistical difference in OS (secondary endpoint) and planned postprogression crossover to bevacizumab (40%) in the chemotherapy arm. Nevertheless, she pointed out that the results are practice changing and bevacizumab with weekly paclitaxel should be considered a new treatment paradigm in platinum-resistant ovarian cancer.
Eur J Cancer. 2013;49(Suppl 3): Abstract LBA5.
ICON6: Cediranib Prolongs Survival in Recurrent Ovarian Cancer
Finally, ICON6 investigated the benefit of adding cediranib to standard platinum-based chemotherapy in patients with relapsed, platinum-sensitive ovarian cancer, and it showed that cediranib significantly improved both median PFS and median OS by approximately 3 months compared with chemotherapy alone. Patients received platinum-based chemotherapy plus either placebo, cediranib (20 mg/day) during chemotherapy followed by placebo for up to 18 months (concurrent regimen), or cediranib (20 mg/day) followed by maintenance cediranib (concurrent + maintenance regimen). Median PFS improved from 9.4 months to 12.6 months, and median OS improved from 17.6 months to 20.3 months. Jonathan Ledermann, MD (University College London Cancer Institute, London, United Kingdom), characterized these results as “ground-breaking.” He pointed out that cediranib is the first oral VEGFR tyrosine kinase inhibitor that has been shown to delay tumor progression and improve OS in recurrent ovarian cancer. Moreover, it is well tolerated with prolonged use. The most common adverse events were hypertension, diarrhea, and fatigue.
Eur J Cancer. 2013;49(Suppl 3): Abstract LBA10.