20 december 2012: het volledige studierapport dat gratis is in te zien van onderstaande studie over Everolimus naast Fulvestrand toegevoegd bij hormoongevoelige borstkanker.

2 augustus 2012: de Telegraaf meldt dat everolimus - afinitor per direct gratis gratis beschikbaar komt voor patiënten met borstkanker in 40 Nederlandse ziekenhuizen omdat Novartis dit medicijn gratis beschikbaar stelt via een zogeheten early access registratie programma. Zie bericht onder gerelateerde artikelen voor meer informatie hierover

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. Hieronder het abstract van de studie: Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. klik hier voor het volledige studierapport dat gratis is in te zien.

The combination of everolimus (Afinitor, Novartis) plus exemestane has produced "the strongest data ever seen in estrogen-receptor -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 , 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.

Everolimus combined with an aromatase inhibitor improved progression-free survival in patients with hormone-receptor-positive advanced breast cancer previously treated with nonsteroidal aromatase inhibitors

N Engl J Med. 2012 Feb 9;366(6):520-9. doi: 10.1056/NEJMoa1109653. Epub 2011 Dec 7.

Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer.

Source

Division of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA. jbaselga@partners.org

Abstract

BACKGROUND:

Resistance to endocrine therapy in breast cancer is associated with activation of the mammalian target of rapamycin (mTOR) intracellular signaling pathway. In early studies, the mTOR inhibitor everolimus added to endocrine therapy showed antitumor activity.

METHODS:

In this phase 3, randomized trial, we compared everolimus and exemestane versus exemestane and placebo (randomly assigned in a 2:1 ratio) in 724 patients with hormone-receptor-positive advanced breast cancer who had recurrence or progression while receiving previous therapy with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat advanced disease (or both). The primary end point was progression-free survival. Secondary end points included survival, response rate, and safety. A preplanned interim analysis was performed by an independent data and safety monitoring committee after 359 progression-free survival events were observed.

RESULTS:

Baseline characteristics were well balanced between the two study groups. The median age was 62 years, 56% had visceral involvement, and 84% had hormone-sensitive disease. Previous therapy included letrozole or anastrozole (100%), tamoxifen (48%), fulvestrant (16%), and chemotherapy (68%). The most common grade 3 or 4 adverse events were stomatitis (8% in the everolimus-plus-exemestane group vs. 1% in the placebo-plus-exemestane group), anemia (6% vs. <1%), dyspnea (4% vs. 1%), hyperglycemia (4% vs. <1%), fatigue (4% vs. 1%), and pneumonitis (3% vs. 0%). At the interim analysis, median progression-free survival was 6.9 months with everolimus plus exemestane and 2.8 months with placebo plus exemestane, according to assessments by local investigators (hazard ratio for progression or death, 0.43; 95% confidence interval , 0.35 to 0.54; P<0.001). Median progression-free survival was 10.6 months and 4.1 months, respectively, according to central assessment (hazard ratio, 0.36; 95% CI, 0.27 to 0.47; P<0.001).

CONCLUSIONS:

Everolimus combined with an aromatase inhibitor improved progression-free survival in patients with hormone-receptor-positive advanced breast cancer previously treated with nonsteroidal aromatase inhibitors. (Funded by Novartis; BOLERO-2 ClinicalTrials.gov number, NCT00863655.).