Approval Sought for Avastin in the Frontline Ovarian Cancer Setting

Avastin (bevacizumab), an angiogenesis inhibitor, was granted a supplemental biologics license application (sBLA) by the FDA for the frontline treatment of women with advanced ovarian cancer, said Genentech, the manufacturer of the drug.

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

“About 80 percent of women with ovarian cancer are diagnosed in the advanced stages when the disease is difficult to treat and options are limited,” Sandra Horning, M.D., 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 3 GOG-0218 trial (1,873 patients).

In the study, women with treatment-naïve stage 3/4 ovarian cancer were randomly assigned to chemotherapy alone with AUC 6 carboplatin and 175 mg/m² of paclitaxel (625 patients), Avastin-initiation from cycle 2 through 7 (625 patients), or Avastin combined with chemotherapy followed by Avastin alone starting at cycle 2 and continuing throughout the study (623 patients). Avastin was administered at 15 mg/kg every three weeks.

Women assigned to the Avastin -continuation group for a total duration of 22 cycles had a median progression-free survival (PFS) of 18.2 months compared with 12 months in women who received chemotherapy alone.

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

In November 2014, the FDA approved Avastin in combination with pegylated liposomal doxorubicin, paclitaxel or topotecan for women with platinum-resistant recurrent ovarian cancer. PFS results from the phase 3 AURELIA trial showed that Avastin was associated with 62 percent improvement in PFS.

In the AURELIA study, 361 patients with platinum-resistant ovarian cancer were randomized in a 1-1 ratio to receive chemotherapy alone (182 patients) or in combination with Avastin (179 patients). The median PFS with Avastin was 6.8 versus 3.4 months with chemotherapy alone. The objective response rate (ORR) was 28 percent versus 13 percent favoring the Avastin arm. Median overall survival (OS) for the Avastin arm was 16.6 months compared with 13.3 months with chemotherapy alone.

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

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

Both studies demonstrated a significant improvement in PFS. In the GOG-0213 study, median PFS improved by 3.4 months with the addition of Avastin to chemotherapy compared to chemotherapy alone (13.8 vs 10.4 months).

Results from OCEANS (484 patients) showed a median PFS improvement of four months for Avastin with chemotherapy versus placebo plus chemotherapy (12.4 vs 8.4 months). The secondary endpoint of OS did not show statistically significant improvement (HR, 0.95).

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