Phase III randomized placebo-controlled trial of two doses of megestrol acetate as treatment for menopausal symptoms in women with breast cancer: Southwest Oncology Group Study 9626

Author(s): Goodwin JW, Green SJ, Moinpour CM, Bearden JD 3rd, Giguere JK, Jiang CS, Lippman SM, Martino S, Albain KS

Affiliation(s): Cancer Research for the Ozarks, 1730 E Republic Rd, Suite V, Springfield, MO 65804, USA. jgoodwin@sprg. mercy. net

Publication date & source: 2008-04-01, J Clin Oncol. 26(10):1650-6.

Publication type: Clinical Trial, Phase III; Multicenter Study; Randomized Controlled Trial; Research Support, N. I.H. Extramural

PURPOSE: Prior progestin studies treating hot flashes in women have been short duration and single dose. This study tests the progestin megestrol acetate (MA) at two doses versus placebo over 6 months. PATIENTS AND METHODS: Patients with T1-3, N0-1, M0 breast cancer were eligible after completion of surgery and chemotherapy and at least 4 months of tamoxifen (if prescribed). Women were required to have at least 10 hot flashes of any severity or at least five severe episodes per week. Patients were randomly assigned to placebo, MA 20 mg, or MA 40 mg for 3 months. Success at 3 months was defined as completion of treatment with a >or= 75% reduction in hot flashes from baseline. If success was achieved, drug treatment for another 3 months was given on the same blinded arm; if not, open-label MA 20 mg was added to blinded study drug and continued for 3 months. Other menopausal symptoms were also assessed. RESULTS: Two hundred eighty eight eligible women were randomly assigned (286 eligible), of whom 85% were on tamoxifen, 40% had over 63 hot flashes/week, and 75% had vasomotor symptoms for >or= 6 months. Success at 3 months was 14% on placebo, 65% on 20 mg, and 48% on 40 mg (both MA doses superior to placebo; P < .0001). Most successes at 3 months were maintained at 6 months (77% on 20 mg and 81% on 40 mg). CONCLUSION: MA significantly reduced vasomotor symptoms with durable benefit over 6 months. MA 20 mg/d is the preferred dose. There was no significant impact on other menopausal symptoms.

Page last updated: 2008-06-22

CONCUR: Regorafenib Active in Asian Patients

In the CONCUR trial of 204 patients, reported by Jin Li, MD, Professor and Director of the Department of Medical Oncology at Fudan University Shanghai Cancer Center, use of regorafenib—an oral multikinase inhibitor that targets pathways involved in tumor growth and progression—was associated with a 45 percent reduction in the risk of death in Asian patients with metastatic colorectal cancer who had disease progression after standard therapy compared with placebo. And approximately half of treated patients experienced a clinical response or stable disease.

CONCUR, which was sponsored by Bayer HealthCare Pharmaceuticals, met its response goals but not the toxicity goals. “Regorafenib needs dose and schedule refinement,” Goldberg said in his discussion of the trial, suggesting dose reductions or a one-week-on one-week-off strategy.

With a median of 10.6 weeks under treatment, about 26 percent of patients had dose reductions and 66 percent had dose interruptions. “The biggest challenge for regorafenib researchers is to find a better way to give this drug so we can exploit its benefit, because there was a relatively high rate of grade 3 and 4 toxicity,” he said. “For those of us who use regorafenib in the clinic, treatment tolerance is the biggest issue we face.”

JIN LI, MD. JIN LI.

RICHARD M. GOLDBERG.

But only 15 percent of patients enrolled in CORRECT were Asian—mostly from Japan—while all patients in CONCUR were from mainland China, Hong Kong, Taiwan, the Republic of Korea, and Vietnam.

Patients who had disease progression after at least two prior lines of standard therapy were randomly assigned to receive oral regorafenib (136 patients) or placebo (68 patients) for the first three weeks of a four-week cycle. Prior anti-VEGF or anti-EGFR was allowed but not required.

The most frequent treatment-emergent adverse effects were hand-foot skin reaction (16% of patients), hypertension (12%), hyperbilirubinemia (12%), elevated liver enzymes (AST 10%, ALT 8%), hypophosphatemia (9%), anemia (7%), and hyperlipasemia (7%). There were no reports of liver failure or pancreatitis.

“What is important [regarding serious adverse events] is that the rate with regorafenib was similar to that of placebo—31.3 percent and 26.5 percent, respectively,” Li said.

Metastatic Colorectal Cancer: TAS-102, Regorafenib Trials Unequivocally Positive

BARCELONA, Spain—Two new entries in the treatment of metastatic colorectal cancer were discussed here at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer, each showing promise in a heavily pretreated population.

The placebo-controlled, randomized, Phase III trials were for regorafenib (CONCUR) and TAS-102 (RECOURSE).

“The good news is, both of these drugs are active, said Richard M. Goldberg, MD, Professor and Physician-in-Chief at Ohio State University James Cancer Hospital and Comprehensive Cancer Center, who was the Discussant for both trials. He called the trials “unequivocally positive.”

Goldberg congratulated the researchers for well-designed trials in appropriate populations that showed significant survival and response benefit for each drug. But toxicities for regorafenib were too high, he said, recommending dose reductions or changes in dosing strategy.