ESMO 2014 - Abstract LBA9

ESMO 2014 Abstract LBA9: Breast Cancer Treatment With Everolimus (EVE) and Exemestane (EXE) for ER+ Women: Results of the 2nd Interim Analysis of the Non-interventional Trial, BRAWO

Fasching, P.A. et al. 

Update on ER+ HER2- Metastatic Breast Cancer

BRAWO is a German non-interventional study of hormone receptor positive (ER+) and HER2- metastatic breast cancer (MBC) treated with the combination of everolimus and exemestane. This phase IV study has the intent of enrolling 3,000 patients across 400 sites in Germany. The primary end-point of this study is both efficacy (as measured by PFS) and the impact of physical activity on efficacy (PFS).

At ESMO 2014, the results of the second pre-planned interim analysis were shown of the first 500 patients enrolled (across 191 sites) with at least 12 months of follow-up prior to data cut-off. The summary of the clinical findings are summarized below:

·    The majority of patients received EVE+EXE as 1st line (26.2%) or 2nd line (28.8%) therapy for MBC

·    Median PFS in BRAWO was consistent with BOLERO-2 in the overall population (8.0 months and 7.8 months, respectively)

·    For patients receiving EVE+EXE as first-line therapy in the advanced setting, the results again were similar to that in BOLERO-2 (10.1 months BRAWO and 11.5 months in BOLERO-2)

·    86.8% of patients received stomatitis prophylactic prevention recommendations from their physician

·    Among these first 500 pts, overall 39.8% developed stomatitis (grade 1, 23.2%; grade 2, 17.0%; grade 3, 3.4%; grade 4, 0.2%)

·    Overall the rate of any adverse event (AE) was lower when EVE+EXE was used earlier in the treatment disease (1st or 2nd line) than when used later (69% vs 81%; p<0.001) – as demonstrated in the 1st interim analyses (ASCO 2014)


CARE Faculty Perspective:

 ·     Efficacious treatment strategies for the management of ER+ HER2- MBC is important as this is the largest subtype cohort seen (in both early and advanced stage disease)

·     The combination of EVE and EXE provides a treatment option for ER+ HER2- MBC with clinically meaningful improvements in PFS over hormonal therapy alone

·     The use of EVE and EXE in a ‘real world’ scenario (as demonstrated in the BRAWO study) reproduces the clinical benefit seen in the original clinical trial (BOLERO-2). This type of demonstration is important as there is a general concern that clinical trial populations may not be truly representative of a general population of MBC patients and thus the associated benefits garnered with the study treatment

·     Earlier use of this combination and effective education and early management of associated toxicities is associated with lower adverse event rates

·     Future targeted therapies (CDK 4/5 inhibitors, PIK3CA inhibitors, AKT inhibitors, HDAC inhibitors…) are generally being studied in combination with hormonal therapy in ER+ MBC, and a need exists to identify predictive biomarkers for response and toxicity to move the field forward towards precision medicine


Stephen Chia, MD

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