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Afinitor® (everolimus) plus exemestane increases progression-free survival (PFS) in breast cancer patients, according to the updated results of a Phase III study presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium (SABCS).
Initial results of BOLERO-2 have been published 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 lead author Gabriel Hortobagyi, Chair of Breast Medical Oncology at the University of Texas MD Anderson Cancer Center.
“Everolimus is the first treatment to enhance the efficacy of hormonal therapy in this patient population, where there remains a significant unmet need.”
Five months on, updated findings from the BOLERO-2 study presented at SABCS showed treatment with everolimus plus hormonal therapy more than doubled PFS to 7.4 months compared to 3.2 months with hormonal therapy alone (hazard ratio=0.44 [95% confidence interval (CI): 0.36 to 0.53]; p<1×10-16) 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 (hazard ratio=0.36 [95% CI: 0.28 to 0.45]; p<1×10-16).
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 favourable 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.
The original results, published in NEJM, 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 ratio=0.43 [95% CI: 0.35 to 0.54]; p<0.001) 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 (hazard ratio 0.36 [95% CI: 0.27 to 0.47]; p<0.001).
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.