Sorafenib Breaks the Silence in Ovarian Cancer Treatment Research

The Lancet Oncologyreported a phase-2 clinical trial conducted in Germany, finding that adding to topotecan chemotherapy sorafenib (brand name Nexavar), an oral targeted cancer drug, improved outcomes in platinum-resistant ovarian cancer in women by improving progression-free survival (the time treatment keeps the disease controlled).

Study details: They had received the chemotherapy platinum as treatment.

This multicenter, double-blind study enrolled 172 ovarian cancer patients. They had previously received 2 or 1 lines of chemotherapy for recurrent ovarian cancer.

Patients were enrolled between 2010 and 2013 and randomly assigned to two arms;

Among patients, 83 received topotecan on days 1-5 at 1.25 mg/m2 plus sorafenib on days 6-15 at 400 mg twice daily, while 89 received placebo instead of sorafenib. Treatment was administered every 21 days for 6 months. Patients whose cancer had not progressed (worsened) continued oral sorafenib or placebo for up to 1 year as maintenance treatment thereafter.

The primary endpoint was progression-free survival (the time treatment keeps the disease controlled).

Study results

• After completing chemotherapy, %42 of the sorafenib group and %38 of the placebo group could receive maintenance treatment.
• Median progression-free survival was 6.7 months with sorafenib and 4.4 months with placebo. Sorafenib reduced progression risk by %40.
• Median overall survival was 17.1 months for sorafenib and 10.1 months for placebo.

Adverse effects

The most common grade 3 or 4 (severe) adverse effects were leukopenia (% 69 versus % 53), neutropenia (% 55 versus % 54), and thrombocytopenia (% 28 versus % 22). Grade 3 hand–foot skin allergy occurred in % 13 of sorafenib patients and none receiving placebo. Grade 2 alopecia (hair loss) was % 29 versus % 13. Adverse effects caused death in 4 sorafenib patients and 5 placebo patients.

In conclusion, in this study, oral sorafenib combined with topotecan and continued as maintenance treatment produced a statistically and clinically meaningful improvement in progression-free survival in women with platinum-resistant ovarian cancer. If supported by a phase-3 trial involving more patients, these findings may change clinical practice for second-line and later treatment of advanced ovarian cancer. Also, given that sorafenib inhibits angiogenesis (new blood vessel formation), chemotherapy and antiangiogenic drug combinations may be considered the backbone of ovarian cancer treatment.

• DRUG RESISTANCE: The Main Factor Complicating Cancer Treatment
• Treatment of Gynecological Cancers
• Innovations in 2017 and 2018