The combination of Afinitor® (everolimus) plus Herceptin® (trastuzumab) paclitaxel appears effective for patients with advanced HER2-positive breast cancer that is hormone receptor (HR)-negative. These findings were presented at the 2014 San Antonio Breast Cancer Symposium, December 9–13, in San Antonio, Texas.

Afinitor is an oral medication that works by inhibiting a protein known as mTOR. The mTOR protein plays an important role in regulating cancer cell division and blood vessel growth. Currently, Afinitor is used for the treatment of selected patients with kidney cancer, pancreatic neuroendocrine tumors, subependymal giant cell astrocytoma (SEGA), renal angiomyolipoma, and hormone receptor-positive/HER2-negative breast cancer. In earlier studies, Afinitor has appeared active against breast cancer when combined with Herceptin and paclitaxel.

To evaluate Afinitor plus Herceptin and paclitaxel as first-line treatment for women with advanced HER2-positive breast cancer, researchers conducted a Phase III trial. They included 719 patients in the study who had advanced HER-positive breast cancer—patients with both HR-negative and HR-positive disease—and had not previously received Herceptin. Patients were randomly assigned to receive either: 1) Afinitor at 10 mg per day plus weekly paclitaxel and Herceptin or 2) placebo (inactive substitute) plus weekly paclitaxel and Herceptin. The researchers’ primary focus was progression-free survival.

Among patients in the study, the median (midpoint) age was 53, 70.5% had metastases, and about 43% had HR-negative disease. At a median follow-up of just over three years, researchers observed the following:

  • Overall (HR negative and HR positive), patients receiving Afinitor lived only a median of half a month longer without progression. Median progression-free survival was 15 months for patients who received Afinitor and 14.5 months for those who received placebo. In other words, progression-free survival was basically the same between both groups.
  • Patients who had HR-negative disease appeared to benefit more from Afinitor. These women had a median progression-free survival that was over seven months longer than HR-negative patients on placebo (20 months versus 13 months, respectively)—a reduction in risk of progression of 34%.
  • Safety for Afinitor in this trial was similar to other studies. Common side effects that occurred more frequently in patients receiving Afinitor versus placebo included stomatitis (inflammation of mouth and lips), diarrhea, and alopecia (hair loss).

The researchers concluded that first-line Afinitor plus paclitaxel and Herceptin did not improve progression-free survival in all patients with HER2-positive advanced breast cancer. The combination was beneficial, however, in patients with HR-negative disease. These findings suggest that Afinitor plus paclitaxel and Herceptin might be effective first-line treatment for patients with HER2-positive advanced breast cancer that is HR negative.

Reference: Hurvitz SA, Andre F, Jiang Z, et al. Phase 3, Randomized, Double-Blind, Placebo-Controlled Multicenter Trial of Daily Everolimus plus Weekly Trastuzumab and Paclitaxel as First-Line Therapy in Women with HER2+ Advanced Breast Cancer: BOLERO-1. Program and Abstracts of the 2014 San Antonio Breast Cancer Symposium; December 9–13, 2014; San Antonio, Texas. Abstract S6-01.

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