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Everolimus combination prolonged PFS in HER-2–positive breast cancer
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The addition of everolimus to trastuzumab and vinorelbine significantly improved PFS in women with trastuzumab-resistant, HER-2–positive advanced breast cancer, according to results of a randomized, double blind, placebo-controlled phase 3 study.
“Disease progression in patients with HER-2–positive breast cancer receiving trastuzumab might be associated with activation of the PI3K/Akt/mTOR intracellular signaling pathway,” the researchers wrote. “We aimed to assess whether the addition of the mTOR inhibitor everolimus to trastuzumab might restore sensitivity to trastuzumab.”
The analysis included 569 women who had previously received taxane therapy. Researchers assigned 284 women to 5 mg daily everolimus (Afinitor, Novartis), weekly 2 m/kg doses of trastuzumab (Herceptin, Genentech) and weekly 25 mg/m2 doses of vinorelbine. The other 285 women received placebo plus trastuzumab and vinorelbine. Treatment was administered in 3-week cycles.
Median follow-up was 20.2 months (interquartile range, 15-27.1).
Researchers reported a median PFS of 7 months (95% CI, 6.74-8.18) in the everolimus arm and 5.78 months (95% CI, 5.49-6.90) in the placebo arm (HR=0.78; 95% CI, 0.65-0.95).
More women in the everolimus arm experienced grade 3 to grade 4 neutropenia (73% vs. 62%), leucopenia (38% vs. 29%), anemia (19% vs. 6%), febrile neutropenia (16% vs. 4%), stomatitis (13% vs. 1%) and fatigue (12% vs. 4%). Serious adverse events also were more common in the everolimus arm (42% vs. 20%). Two patients in each arm died due to treatment-related adverse events.
“The addition of everolimus to trastuzumab plus vinorelbine significantly prolongs PFS in patients with trastuzumab-resistant and taxane-pretreated HER-2–positive breast cancer,” the researchers concluded. “The clinical benefit should be considered in the context of the adverse event profile in this population.”
Disclosure: The study was funded by Novartis Pharmaceuticals Corporation.
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