Cediranib plus chemotherapy prolonged PFS, OS in ovarian cancer

The addition of cediranib to chemotherapy significantly improved PFS in patients with recurrent ovarian cancer, according to results of an international, randomized, phase 3 study presented at the European Cancer Congress.

Cediranib (AZD2171, Recentin; AstraZeneca), which inhibits VEGF signaling and is active against all three VEGF receptors, also extended PFS and OS when used as maintenance therapy, researchers said.

In prior studies, cediranib demonstrated single-agent activity and manageable toxicity in patients with ovarian cancer.

The ICON6 trial included 456 patients who were treated at 63 centers. All patients had an ECOG performance status of 0 or 1. The median age in the cohort was 62 years. The majority of patients (67%) underwent no treatment within the prior 12 months.

All patients received up to six cycles of chemotherapy. Chemotherapy regimens included platinum/paclitaxel, carboplatin/cisplatin alone, or platinum/gemcitabine gemcitabine (Gemzar, Eli Lilly).

Researchers randomly assigned patients in a 2:3:3 ratio to one of three treatment arms:

• chemotherapy plus placebo;
• concurrent cediranib and chemotherapy, followed by maintenance placebo; or
• concurrent cediranib and chemotherapy, followed by maintenance cediranib.

Cediranib was administered in 20 mg daily doses.

Baseline characteristics were balanced between the three arms.

PFS served as the primary endpoint. Secondary endpoints included OS, toxicity and quality of life. Researchers calculated PFS and OS with restricted means.

Patients assigned to concurrent cediranib and chemotherapy followed by maintenance cediranib demonstrated longer PFS (12.6 months vs. 9.4 months) and OS (20.3 months vs. 17.6 months) compared with those assigned to chemotherapy plus placebo (HR=0.70; P=.0419).

Patients assigned to concurrent cediranib and chemotherapy followed by maintenance placebo also demonstrated longer PFS compared with those treated with chemotherapy plus placebo (11.4 months vs. 9.4 months; HR=0.68; P=.0022)

“Cediranib given concurrently with platinum-based chemotherapy improves PFS and, when continued as maintenance, significantly improves both progression-free and overall survival in women with recurrent ovarian cancer,” the researchers concluded.

Researchers observed significantly increased incidence of adverse effects in the cohort assigned to cediranib maintenance. Adverse effects included hypertension, diarrhea, hypothyroidism, hoarseness, hemorrhage, proteinuria and fatigue.

For more information:

Ledermann JA. Abstract #10. Presented at: The European Cancer Congress 2013; Sept. 27-Oct. 2, 2013; Amsterdam.

Disclosure: See the study for a full list of the researchers’ relevant financial disclosures.