Everolimus (Afinitor) samen met exemestane geeft significant langere ziektevrije tijd voor vrouwen met hormoongevoelige borstkanker, ook waar sprake was van resistentie voor Arimidex en Femara. Artikel geplaatst 27 september 2011
27 september 2011: bron: Medscape
Vrouwen met hormoongevoelige borstkanker maar resistent voor arimidex en/of femara lijken nu toch nog een andere optie te krijgen. Everolimus gegeven naast fulvestrand - exemestane blijkt bijzonder goed aan te slaan. Uit een gerandomiseerde fase III studie blijkt dat de ziektevrij tijd werd verlengd van 2,8 maanden naar 6,9 maanden in vergelijking met alleen exemestane bij die vrouwen waar de behandeling aansloeg. De respons voor de combinatie behandeling ging van 0,4% naar 9,6%. Dit lijkt niet veel maar als 1 op de 10 vrouwen die uitbehandeld leken alsnog een effectieve aanpak kunnen krijgen dan is dat toch goed te noemen. Overigens heeft everolimus ook al bij gevorderde nierkanker waar andere middelen faalden en bij de ziekte van Waldenström bewezen een uitstekend middel te zijn. Hier een gedeelte uit een artikel van medscape over de recente studie gepresenteerd op het EMCC gisteren.
The combination of everolimus (Afinitor, Novartis) plus exemestane has produced "the strongest data ever seen in estrogen-receptor [ER]-positive breast cancer
Source: Medscape
The results from this large phase 3 trial show that "everolimus is the first agent to enhance hormone therapy in refractory ER-positive breast cancer patients," and they represent a "paradigm shift in the management of these patients," he told delegates.
The BOLERO-2 study was conducted in 724 postmenopausal women with ER-positive but HER2-negative advanced breast cancer who had previously been treated with and had become refractory to the nonsteroidal aromatase inhibitors letrozole and anastrozole. Previous therapies included tamoxifen (in 48% patients), fulvestrant (in 16%), and chemotherapy (in 68%).
"When patients stop responding to hormonal therapy, the benefits from any secondary therapy are limited," Dr. Baselga explained.
All of the women in the study received exemestane, which is a steroidal aromatase inhibitor with a slightly different profile than letrozole or anastrozole. In addition, women were randomized in a 2:1 ratio to receive everolimus (10 mg/day orally).
A preplanned interim analysis found that everolimus significantly improved progression-free survival, the primary end point of the study. Median progression-free survival, assessed by local investigators, was longer with everolimus plus exemestane than with exemestane alone (6.9 vs 2.8 months; hazard ratio [HR], 0.43; P ≤ .0001). These figures changed slightly after central assessment (10.6 vs 4.1 months; HR, 0.36; P < .0001).
These results were highly significant, Dr. Baselga emphasized. "This is a very uncommon result in metastatic disease," he said at a press briefing. "Very seldom do you see such an effect."
In addition, there was a significantly greater response rate (9.5% vs 0.4%) and clinical benefit (33.4% vs 18.0%) in the combination group. Dr. Baselga noted that these data are immature and likely to improve.
The most common adverse effects reported in the combination and exemestane-alone groups were stomatitis (8% and 1%, respectively), anemia (5% and 1%), dyspnea (4% and 1%), hypoglycemia (4% and <1%), fatigue (3% and 1%), and pneumonitis (3% and 0%).
"The safety profile is consistent with previous everolimus experience," Dr. Baselga explained.
In a statement from the manufacturer, Novartis Oncology president Herve Hoppenot said: "Everolimus is the first drug to show significant efficacy when combined with hormone therapy in ER-positive and HER2-negative breast cancer, where there continues to be a critical unmet need."
"The magnitude of benefit seen in these patients, despite their resistance to previous hormonal therapies, shows that everolimus represents a potential important new treatment approach," he added.
This BOLERO-2 trial was funded by Novartis. Dr. Baselga reports acting as a consultant for many pharmaceutical companies, including Novartis, Roche, Merck SA, and Bayer.
2011 European Multidisciplinary Cancer Congress (EMCC): Abstract 9LBA. Presented September 26, 2011.
