sBLA for Bevacizumab in First-Line Ovarian Cancer Accepted by FDA

Sandra Horning, MD

Sandra Horning, MD

A supplemental biologics application (sBLA) for bevacizumab (Avastin) has been accepted by the FDA for the first-line treatment of advanced ovarian cancer, according to Genentech, the manufacturer of the angiogenesis inhibitor.

The FDA is expected to render a decision on the sBLA by June 25, 2018. The new indication would make frontline bevacizumab available in combination with carboplatin and paclitaxel, followed by bevacizumab alone, for women with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer.

“About 80% of women with ovarian cancer are diagnosed in the advanced stages when the disease is difficult to treat and options are limited,” Sandra Horning, MD, Genentech’s chief medical officer and head of Global Product Development, said in a press release. “We are committed to working closely with the FDA to bring this potential new treatment option to women with newly diagnosed advanced ovarian cancer as soon as possible.”

The sBLA is based on results from the pivotal, multicenter, randomized, double-blind, placebo-controlled phase III GOG-0218 trial (N = 1873).

In the study, women with treatment-naïve stage III/IV ovarian cancer were randomly assigned to chemotherapy alone with AUC 6 carboplatin and 175 mg/m²of paclitaxel (n = 625), bevacizumab-initiation from cycle 2 through 7 (n = 625), or bevacizumab combined with chemotherapy followed by bevacizumab alone starting at cycle 2 and continuing throughout the study (n = 623). Bevacizumab was administered at 15 mg/kg every 3 weeks.

Women assigned to the bevacizumab-continuation group for a total duration of 22 cycles had a median progression-free survival (PFS) of 18.2 months compared with 12.0 months in women who received chemotherapy alone (hazard ratio [HR], 0.64; 95% CI, 0.54 -0.77,P<.0001).¹

Genentech said adverse events (AEs) in the trial were consistent with those seen in previous bevacizumab studies.

In November 2014, the FDA approved bevacizumab in combination with pegylated liposomal doxorubicin, paclitaxel, or topotecan for women with platinum-resistant recurrent ovarian cancer. PFS results from the phase III AURELIA trial showed that bevacizumab was associated with 62% improvement in PFS.²

In the AURELIA study, 361 patients with platinum-resistant ovarian cancer were randomized 1:1 to receive chemotherapy alone (n = 182) or in combination with bevacizumab (n = 179). The median PFS with bevacizumab was 6.8 versus 3.4 months with chemotherapy alone (HR, 0.38; 95% CI, 0.30-0.49;P<.0001). The objective response rate (ORR) was 28% versus 13% favoring the bevacizumab arm. Median overall survival (OS) for the bevacizumab arm was 16.6 months compared with 13.3 months with chemotherapy alone (HR, 0.89; 95% CI, 0.69-1.14;P= not significant).

The FDA approved bevacizumab in December 2016 for use in combination with carboplatin and paclitaxel or carboplatin and gemcitabine, followed by single-agent bevacizumab, for the treatment of patients with platinum-sensitive recurrent ovarian cancer.

The approval was based on results from 2 randomized controlled phase III studies, GOG-0213 and OCEANS.³GOG-0213 demonstrated that adding bevacizumab to chemotherapy led to a non-statistically significant 5-month improvement in median OS compared with chemotherapy alone (42.6 vs 37.3 months; HR, 0.84).

Both studies demonstrated a significant improvement in PFS. In the GOG-0213 study, median PFS improved by 3.4 months with the addition of bevacizumab to chemotherapy compared to chemotherapy alone (13.8 vs 10.4 months; HR, 0.61; 95% CI, 0.51-0.72).

Results from OCEANS (N = 484) showed a median PFS improvement of 4 months for bevacizumab with chemotherapy versus placebo plus chemotherapy (12.4 vs 8.4 months; HR, 0.46, 95% CI, 0.37-0.58;P<.0001). The secondary endpoint of OS did not show statistically significant improvement (HR, 0.95).

In both trials, the bevacizumab-containing regimens resulted in superior objective response. The ORR with bevacizumab was 78% in both studies compared with 56% in GOG-0213 and 57% in OCEANS for the chemotherapy arms.

References:

1. FDA Accepts Genentech&rsquo;s Supplemental Biologics License Application for Avastin as a Front-Line Treatment for Women with Advanced Ovarian Cancer. Genentech. http://bit.ly/2i548hf. Accessed October 26, 2017.
2. FDA Approves Genentech&rsquo;s Avastin (Bevacizumab) Plus Chemotherapy to Treat Women with Platinum-Resistant Recurrent Ovarian Cancer. Genentech. http://bit.ly/2z9buev. Accessed October 26, 2017.
3. FDA Approves Genentech&rsquo;s Avastin^&reg;(Bevacizumab) Plus Chemotherapy for a Specific Type of Advanced Ovarian Cancer. Genentech. http://bit.ly/2h2DQeB. Accessed October 26, 2017.