1. SABCS 2011 BOLERO-2 Updated Results
Everolimus for postmenopausal women with advanced breast cancer: updated results of the BOLERO-2 phase III trial Presented by Dr. Gabriel Hortobagyi
Reviewer: Dr. Sunil Verma
Date posted: December 12th, 2011

2. BACKGROUND
The average survival of patients with Metastatic Breast Cancer (MBC) remains around months.
The general approach is to treat metastatic HR+ve MBC with sequential anti-estrogen agents
Though some patients may have a durable response, most patients will develop resistance to these agents and many go on to receive salvage chemotherapy
One of the key pathways of resistance is the pI3k-AKT pathway and hence mTor inhibitors such as Everolimus may be ideal agents to help overcome this resistance

3. R BOLERO-2 Treatment B: exemestane + placebo (n=239) Randomized 2:1
N= 724 ER+, previously non-steroidal aromatase inhibitor treated MBC patients
Primary Outcome: Progression Free Survival
Baseline characteristics were well balanced; median age was 62 years; 56% had visceral involvement and 84% were sensitive to prior hormone therapy. Prior therapy included letrozole or anastrozole (100%), tamoxifen (48%), fulvestrant (16%) and chemotherapy for metastatic disease (25%).
Treatment A:
exemestane (EXE) + everolimus (EVE) (n=485) R
Treatment B:
exemestane + placebo (n=239)
Randomized
2:1

4. RESULTS Median follow up of 12.5 months EVE + EXE PBO + EXEHR
p-value
PFS (interim analysis)
(median, months)
7.4
3.2
0.44
(95% CI: )
<1 x 10-16
PFS (central assessment)
11.0
4.1
 0.36
(95% CI: )
Overall survival
interim analysis planned after 182 deaths (December 2011)
23.1% in everolimus arm
29.3% in placebo arm

5. BOLERO-2 Key Conclusions
The addition of Everolimus to Exemestane leads to a substantial improvement in PFS
OS Data is premature
Main Toxicity Events
Stomatitis (Grade 3 – 8%)
Pneumonitis (Grade 3 – 3%)
Rash
No improvement in Quality of Life

6. BOLERO-2 Bottom Line for Oncologists
This is one of the most significant trials in the management of breast cancer
The differences seen in progression free survival are clinically meaningful and will help delay the use of chemotherapy for our patients
This approach may not be suitable for some HR+ve MBC, such as patients with durable response with first line NSAI, slow growing indolent disease or frail/elderly patients. We still need to consider chemotherapy for some patients who have very aggressive disease despite HR+ve status
The toxicity is concerning and we need to be aware and be educated on the management of stomatitis and monitoring for pneumonitis and hyperglycemia prior to the use of this agent in clinical practice