BIBF 1120 as Maintenance Therapy in Relapsed Ovarian Cancer Shows Potential Improvement in Progression Free Survival in a Phase II Trial

September 2, 2011

A phase II trial of BIBF 1120 (Vargatef) in women with relapsed ovarian cancer that were previously treated with chemotherapy showed that BIBF 1120 given as maintenance therapy resulted in improved progression-free survival rates.

Results of a phase II trial studying BIBF 1120 (Vargatef) in women with relapsed ovarian cancer who were previously treated with chemotherapy showed that BIBF 1120 given as maintenance therapy at 250 mg twice a day continuously for 36 weeks resulted in progression-free survival (PFS) rates of 16.3% compared to 5% for the placebo group (hazard ratio, 0.65; P = .06).

The results were published ahead of print last week by Jonathan A. Lederman, MD and colleagues in the Journal of Clinical Oncology (doi: 10.1200/JCO.2010.33.5208).

An ovarian cancer as seen on CT. Source: James Heilman, MD, Wikimedia Commons

Ovarian cancer is particularly problematic to treat and diagnose. Ovarian cancer is often only diagnosed when it is already a late-stage cancer because there are no early detection screening methods and because many of the symptoms are not specific to ovarian cancer and are not always gynecological. If ovarian cancer is found early, the five-year survival rate is 92%. However, only 20% of ovarian cancers are detected at an early stage.

Ovarian cancer is the leading cause of death from gynecological cancers in the United States and the fifth leading cause of cancer death among American women. Approximately 13,580 women in the United States died of the disease in 2010.

The current trial evaluated 83 women with advanced-stage ovarian cancer who had responded to standard of care chemotherapy but were assessed to be high-risk for early recurrence (12 months or less following chemotherapy treatment). The median time on the drug was 2.8 months.

Dose reductions, from 250 mg twice daily to 150 mg, were made in 15 patients in the BIBF 1120 group and were due to hepatotoxicities, diarrhea, and nausea. Most adverse events to the drug were mild and included fatigue, abdominal pain, nausea, diarrhea, and vomiting. Grade 3 and 4 adverse events were similar in both groups-BIBF 1120 group (34.9%), placebo group (27.5%). BIBF 1120 patients were more likely to have liver function test abnormalities.

This phase II trial was designed to test whether BIBF 1120 prolongs the PFS interval after completion of chemotherapy for relapsed ovarian cancer. The authors reasoned that the efficacy of BIBF 1120 as maintenance therapy would be detectable in a small number of patients because this population subset has a high rate of early events. The study did not reach its assumption that the 36-week PFS would be 70% in the treatment group, however, the hazard ratio of 0.65 suggests that “BIBF has activity in this group of patients that merits further investigation.”

Four patients in the BIBF 1120 arm elected to continue treatment with two patients staying on treatment for over a year and one patient that was on the treatment at time of publication, suggesting that prolonged maintenance with BIBF 1120 could have therapeutic benefit that is significant.

BIBF 1120 works by inhibiting vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptors (PDGFRs), and fibroblast growth factor receptors (FGFRs). These receptors are all intricately involved in the formation of blood vessels that are necessary for tumor growth and cancer progression.

BIBF 1120 is currently in a phase III, large-scale, 1,300-patient clinical trial to test whether BIBF 1120 in combination with carboplatin and paclitaxel chemotherapy increases the PFS of ovarian cancer patients with advanced disease that have not had prior treatments. The trial is expected to have data by 2014. BIBF 1120 is also in clinical trials for colorectal cancer, hepatocellular carcinoma, a phase III trial for non-squamous small-cell lung cancer, glioblastoma multiforme, endometrial cancers, as well as phase I trials testing the drug in combination with other treatments.