Bevacizumab Plus Chemotherapy Improves Response Rates and PFS in Platinum-Resistant Ovarian Cancer

An exploratory analysis of the phase III AURELIA trial affirms the benefit of adding bevacizumab to chemotherapy for patients with platinum-resistant recurrent ovarian cancer, according to results presented at the 2012 European Society of Medical Oncology (ESMO) Congress in Vienna, Austria.

The addition of bevacizumab improved response rates and progression-free survival (PFS) when combined with each of 3 different chemotherapy regimens.

“Bevacizumab combined with chemotherapy should be considered a new standard option for platinum-resistant recurrent ovarian cancer,” said Andres M. Poveda, MD, Fundacion Instituto Valenciano de Oncologia in Valencia, Spain, who was lead author of the study.

In the trial, 361 patients with platinum-resistant ovarian cancer who had been treated with up to 2 prior chemotherapy regimens were randomized to receive either weekly paclitaxel (n=115), pegylated doxorubicin (PLD) (n=126), or topotecan (n=120). Within each of those cohorts, patients received the chemotherapy plus bevacizumab or the selected chemotherapy alone. Treatment was continued until unacceptable toxicity or progressive disease occurred.

Analysis of PFS according to type of chemotherapy showed the most robust benefits in the weekly paclitaxel cohort. The median PFS among patients who received bevacizumab added to weekly paclitaxel was 10.4 months versus 3.9 months for weekly paclitaxel alone (HR=0.46; 95% confidence interval [CI], 0.30—0.71). In the PLD cohort, the median PFS was 5.4 months versus 3.5 months, respectively (HR=0.57; 95% CI, 0.39–0.83). In the topotecan cohort, median PFS was 5.8 months versus 2.1 months, respectively (HR=0.32; 95% CI, 0.21–0.49).

Baseline characteristics were well balanced between the treatment arms. Median age was around 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.

Response rates for all three chemotherapy options were superior with the addition of bevacizumab, with the highest overall response rates (ORR) observed in the weekly paclitaxel cohort. In that cohort, the ORR was 51.7% in patients who received paclitaxel plus bevacizumab versus 28.8% for paclitaxel alone. In the PLD cohort, the ORR was 18.3% in the PLD plus bevacizumab arm and 7.9% in the PLD alone arm, and in the topotecan cohort, the ORR was 22.8% in the bevacizumab arm and 3.3% in the topotecan alone arm.

No significant differences in toxicity were observed, with the exception of a higher rate of grade 2 peripheral neuropathy in the weekly paclitaxel cohort (35% vs 22% with chemotherapy alone) and a higher rate of hand-foot syndrome in the PLD cohort (27% vs 14% with chemotherapy alone). Poveda said that these side effects may be explained by longer duration of chemotherapy exposure, which is also associated with longer median PFS.

These results led Nicoletta Colombo, MD, University of Milan Bicocca, European Institute of Oncology in Milan, Italy and formal discussant of the trial, to emphasize the activity of the weekly paclitaxel plus bevacizumab cohort.

“At 6 months, 69% of patients were progression-free, and at 12 months, 33% were progression-free [in the weekly paclitaxel arm],” Colombo said. “This convinces me of the activity of this combination with bevacizumab. My conclusion is that the effect of bevacizumab is seen with any of the chemotherapy regimens studied, but weekly paclitaxel plus bevacizumab seems most promising in terms of response rate and PFS, particularly in this patient population.”

In her discussion of the study, Colombo commended AURELIA for its strengths, saying that it is the only positive trial in patients with platinum-resistant recurrent ovarian cancer. However, she also said that the trial should have included a single-agent bevacizumab arm.

Colombo suggested that the combination of weekly paclitaxel plus bevacizumab should be explored earlier in the course of disease, since the combination is so active in platinum-resistant ovarian cancer.

Poveda AM, Selle F, Hilpert F, et al. Weekly paclitaxel, pegylated liposomal doxorubicin or topotecan ± bevacizumab in platinum-resistant ovarian cancer: analysis by chemotherapy cohort in the GCIG AURELIA randomised phase III trial. Presented at: European Society of Medical Oncology 2012 Congress; September 28 — October 2, 2012; Vienna, Austria. Abstract LBA26.

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