The FINANCIAL -- Updated
results of a Phase III study of Afinitor tablets plus
exemestane, a hormonal therapy, show everolimus provided additional time
women with advanced breast cancer lived without their disease
The study findings, which represent an additional five months of follow-up, were presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, abstract.
Simultaneously, initial results of BOLERO-2 were published in The New England Journal of Medicine and were first presented at the 2011 European Multidisciplinary Cancer Congress .
Updated findings from the BOLERO-2 study presented at SABCS showed treatment with everolimus plus hormonal therapy more than doubled progression-free survival to 7.4 months compared to 3.2 months with hormonal therapy alone 95% confidence interval: by local investigator assessment. Twelve month estimates of patients without disease progression were 31% and 10% in the everolimus and exemestane, and exemestane-alone arms, respectively. An additional analysis based on an independent central radiology review showed everolimus extended PFS to 11.0 months compared to 4.1 months.
Response rates and clinical benefit rates were higher in the combination arms, 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 and are supportive of previously presented outcomes.
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 by local investigator assessment. Additional analysis by an independent central radiology review committee showed everolimus extended PFS to 10.6 months compared to 4.1 months.
The side effects observed were consistent with those previously reported with everolimus with the most common Grade 3 or 4 adverse events including: stomatitis, anemia, hyperglycemia, dyspnea , fatigue and pneumonitis 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.