New Aromatase Inhibitor Compared With Megestrol in Advanced Breast Cancer

Results of a phase III multicenter European study reported ina recent issue of the European Journal of Cancer demonstrate thatanastrozole (Arimidex), a new aromatase inhibitor, in doses of1 and 10 mg orally once daily, is an effective treatment for advancedbreast cancer in postmenopausal women whose disease has progressedfollowing therapy with tamoxifen (Nolvadex). Results of this studycombined with a US study were the basis for the December 27, 1995,FDA clearance for 1-mg anastrozole tablets.

The phase III trial investigated the efficacy and tolerabilityof two blinded doses of anastrozole compared to megestrol acetateat its recommended therapeutic dose (40 mg four times daily) inthe treatment of postmenopausal women with advanced breast cancer.Of the 378 patients enrolled in the study, 135 were randomizedto 1 mg of anastrozole, 118 to 10 mg of the new drug, and 125to megestrol.

Clinical Benefit

After a median follow-up of 6.1 months, there were no statisticallysignificant differences between either dose of anastrozole andmegestrol acetate in terms of objective tumor response rate andtime to objective disease progression.

Approximately one-third of the patients had either an objectiveresponse (complete or partial response) or stabilization of theirdisease for more than 24 weeks. The sites of metastatic diseasewere similar across treatment groups; approximately 40% of thepatients had soft-tissue metastases, 60% had bone metastases,and 40% had visceral (20% liver) metastases. Some patients hadmore than one disease site. Of patients who had a complete orpartial response to anastrozole, 74% continued to respond formore than 24 weeks.

Low Incidence of Weight Gain With Anastrozole

Of the women in the study who were treated with megestrol, 8%experienced drug-related weight gain of at least 5% to 10%, whichwas significantly greater than the incidence of this side effectin those treated with either dose of anastrozole (2.2% for the1-mg dose and 3.4% for the 10-mg dose). In addition, 4.8% of thewomen treated with megestrol experienced thromboembolic disease,compared with 0.9% of the patients on 10 mg of anastrozole and3.7% of those on 1 mg.

"The results of this study confirm the efficacy of Arimidexin treating patients with advanced breast cancer. In addition,the trial indicates that Arimidex provides well-tolerated therapy,"says Paul Plourde, MD, Senior Director of Clinical Research, ZenecaPharmaceuticals.

Tolerability

The most frequently reported side effects considered to be drug-relatedby the investigators were weight gain (8%) and dyspnea (5.6%)in patients treated with megestrol acetate. In addition to weightgain reported as a side effect among patients given megestrol,an actual weight gain of at least 5% was recorded in 35% of thesepatients and a 10% gain was recorded in 12%.

"Prospectively planned analyses demonstrated that patientson megestrol acetate had significant weight gain," reportsDr. Plourde. "In addition, this weight gain continued inpatients who remained on megestrol acetate for longer periodsof time."

Most commonly reported side effects of anastrozole in combinedstudies (this study and a US study), included headache, hot flushes,nausea, asthenia, pain, and back pain.

In the US, anastrozole is indicated for the treatment of advancedbreast cancer in postmenopausal women whose disease has progressedfollowing tamoxifen therapy. Patients with estrogen-receptor-negativedisease and patients who do not respond to tamoxifen rarely respondto anastrozole.