Bevacizumab PFS Benefit Extends Across Cohorts in AURELIA Trial

Andrés M. Poveda, MD

An exploratory analysis of the phase III AURELIA trial demonstrated that adding bevacizumab (Avastin) to chemotherapy in patients with platinum-resistant ovarian cancer benefited patients across treatment cohorts.

Data from the study showed that the addition of bevacizumab improved response rates and progression-free survival (PFS) when combined with each of three different assigned chemotherapy regimens, with paclitaxel demonstrating the most striking results, according to findings presented at the European Society for Medical Oncology (ESMO) 2012 Congress.¹

The AURELIA study accrued 361 patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer previously treated with at least four cycles of platinum-based chemotherapy whose disease had progressed within six months of their last platinum therapy treatment.

Based on their previous treatment experience, patients were first assigned standard chemotherapy with weekly paclitaxel (n = 115), topotecan (n = 120), or pegylated liposomal doxorubicin (PLD; n =126). Patients were then randomized 1:1 to receive chemotherapy alone (n = 182) or combination therapy with bevacizumab (n = 179). Treatment was continued until unacceptable toxicity or progressive disease occurred.

Baseline characteristics were well balanced between the treatment arms. Median age was about 60 years and about 90% had stage III/IV disease. Minor differences were observed, including higher number of prior regimens in the weekly paclitaxel groups.

Table. Cohort Analysis in AURELIA Trial¹

PAC (N = 115)

PLD (N = 126)

TOP (N = 120)

CT(n = 55)

BEV + CT (n = 60)

CT (n = 64)

BEV + CT (n = 62)

CT (n = 63)

BEV + CT (n =57)

PFS (median, mo)

3.9

10.4

3.5

5.4

2.1

5.8

HR (95% CI)^a

0.46 (0.30-0.71)

0.57 (0.39—0.83)

0.32 (0.21-0.49)

ORR, %

28.8

51.7

7.9

18.3

3.3

22.8

Difference (95% CI)

22.9 (3.9—41.8)

10.4 (—2.4 to 23.2)

19.5 (6.7—32.3)

Bev indicates bevacizumab; CI, confidence interval; CT, chemotherapy; HR, hazard ratio; ORR, overall response rate; PAC, paclitaxel; PFS, progression-free survival; PLD, pegylated liposomal doxorubicin; TOP, topotecan.

In the overall results presented at the ASCO 2012 Annual Meeting, median PFS was 6.7 months for bevacizumab plus chemotherapy versus 3.4 months for chemotherapy alone. Based on these results, “Bevacizumab combined with chemotherapy should be considered a new standard option for platinum-resistant recurrent ovarian cancer,” said lead author Andrés M. Poveda, MD, Fundación Instituto Valenciano de Oncología (IVO), Valencia, Spain.

The analysis presented at ESMO showed that the PFS improvement discussed at ASCO extended across treatment groups. However, the most robust benefit occurred with paclitaxel: median PFS of 10.4 months when bevacizumab was added to weekly paclitaxel versus 3.9 months for weekly paclitaxel alone. In the PLD cohort, median PFS was 5.4 months versus 3.5 months, respectively. In the topotecan cohort, median PFS was 5.8 months versus 2.1 months, respectively.

The overall response rate (ORR) for all three chemotherapy options was superior with the addition of bevacizumab, with the highest response rates observed in the weekly paclitaxel cohort: 51.7% versus 28.8% for chemotherapy alone. ORR in the other two cohorts was 18.3% and 7.9%, respectively, for the PLD cohort and 22.8% and 3.3%, respectively, for the topotecan cohort.

No significant differences in toxicity were observed, with the exception of more peripheral neuropathy in the weekly paclitaxel cohort and more hand-foot syndrome in the PLD cohort.

REFERENCE

1. Poveda AM, Selle F, Hilpert F, et al. Weekly paclitaxel (PAC), pegylated liposomal doxorubicin (PLD) or topotecan (TOP) ± bevacizumab (BEV) in platinum (PT)-resistant recurrent ovarian cancer (OC): analysis by chemotherapy (CT) cohort in the GCIG AURELIA randomised phase III trial. Paper presented at: 37th European Society for Medical Oncology Congress; September 28-October 2, 2012; Vienna, Austria. Abstract LBA26.