Updated data from Novartis Afinitor plus everolimus Phase III study on advanced breast cancer

Updated results of a Phase III study of Afinitor® (everolimus) tablets plus exemestane, a hormonal therapy, show everolimus provided additional time women with advanced breast cancer lived without their disease progressing (progression-free survival).

The study findings, which represent an additional five months of follow-up, were presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS). Simultaneously, initial results of BOLERO-2 were published today in The New England Journal of Medicine (NEJM) and were first presented at the 2011 European Multidisciplinary Cancer Congress (EMCC).

"These data provide longer-term evidence of the benefit of adding everolimus to hormonal therapy in patients whose disease progressed while on or following initial hormonal treatment, representing a major paradigm shift in the management of ER+HER2- breast cancer," said Gabriel Hortobagyi, MD, Chair of Breast Medical Oncology, University of Texas MD Anderson Cancer Center and lead study author. "Everolimus is the first treatment to enhance the efficacy of hormonal therapy in this patient population, where there remains a significant unmet need."  

Updated findings from the BOLERO-2 study presented at SABCS showed treatment with everolimus plus hormonal therapy more than doubled progression-free survival (PFS) to 7.4 months compared to 3.2 months with hormonal therapy alone (hazard).

Response rates and clinical benefit rates (patients with complete response, partial response, or stable disease for greater than six months) were higher in the combination arms (12.0% vs. 1.3% and 50.5% vs. 25.5%; p<0.0001), respectively. The results with everolimus were favorable regardless of the presence of visceral disease, prior use of chemotherapy or number of prior therapies. In addition, patients with only bone metastases benefited from the combination. These results represent an additional five months of follow-up (median duration of follow-up of 17.5 months) and are supportive of previously presented outcomes.

"Despite the significant progress in treating women with breast cancer, there have been no new treatment advances for women living with ER+HER2- advanced breast cancer in more than 15 years," said Herve Hoppenot, President, Novartis Oncology. "The results of BOLERO-2 are the first to show everolimus combined with hormonal therapy enabled women with this type of breast cancer to live significantly longer without their tumor progressing."

The original results published in NEJM today showed that at a pre-planned interim analysis, BOLERO-2 met its primary endpoint of PFS showing treatment with everolimus plus hormonal therapy extended PFS to 6.9 months compared to 2.8 months with hormonal therapy alone (hazard).

The side effects observed were consistent with those previously reported with everolimus with the most common Grade 3 or 4 adverse events including: stomatitis (8% vs. 1%), anemia (7% vs. 1%), hyperglycemia (5% vs. <1%), dyspnea (4% vs. 1%), fatigue (4% vs. 1%) and pneumonitis (3% vs. 0%) for the combination and exemestane-only arms, respectively. At the time of updated analysis, 137 patients died, constituting 17.2% of patients in the everolimus plus exemestane arm and 22.7% of those in the exemestane-only arm.

Hormonal therapy remains the cornerstone of treatment for women with advanced breast cancer but almost all patients who respond eventually develop resistance. Everolimus targets the mTOR pathway in cancer cells. mTOR is a protein that acts as an important regulator of tumor cell division, blood vessel growth and cell metabolism. Resistance to hormonal therapy in breast cancer has been associated with over-activation of the mTOR pathway.

Each year, around 220,000 women globally will be diagnosed with ER+HER2- advanced breast cancer. Everolimus is also being investigated for the treatment of patients with HER2+ advanced breast cancer.

Regulatory submissions for everolimus based on the BOLERO-2 results are planned by the end of 2011.

Source:

Novartis

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