2 Landmark Trials Suggest Changes in Practice; Brachytherapy Controversy Attracts Attention

Maurie Markman, MD
Published: Monday, Feb 20, 2012
Maurie Markman, MD

Maurie Markman, MD

Editor-in-Chief of OncologyLive

Senior vice president for Clinical Affairs and National Director for Medical Oncology

Cancer Treatment Centers of America, Eastern Regional Medical Center

As in previous years, the 2011 CTRC-AACR San Antonio Breast Cancer Symposium was associated with a number of important presentations and an element of controversy. This commentary will highlight 2 highly clinically relevant abstracts that discussed the results of phase III randomized trials likely to substantially impact standard management of breast cancer, and a retrospective review of a large national database that has been strongly criticized based on its overall conclusions.

BOLERO-2 Results Support Benefit for Everolimus Plus Exemestane Regimen

In the BOLERO-2 randomized phase III trial, investigators compared single-agent exemestane with the hormonal agent combined with the mTOR inhibitor everolimus.1 A total of 724 hormone receptor-positive postmenopausal women with metastatic breast cancer were treated in this landmark placebo-controlled study. Patients randomized to the combination regimen experienced more than a doubling in the median time to subsequent disease progression (7.4 mo vs 3.2 mo; hazard ratio [HR], 0.44; P <1 x 10-16) compared with the exemestane control group.

Further, the percentage of individuals classified as having achieved “clinical benefit” from the treatment regimen (defined as complete response, partial response, or stable disease lasting for longer than 6 mo) also doubled (50.5% vs 25.5%) in the everolimus plus exemestane arm compared with the control regimen. It remains premature to make any statement regarding the impact of this innovative management strategy on overall survival, but these data are awaited with considerable interest.

Finally, and of considerable importance for a strategy designed to optimize the quantity as well as the quality of life, this unique combination regimen was reasonably well tolerated, although clearly more toxic than hormonal therapy alone (grade 3-4 adverse events: fatigue [4% vs 1%]; stomatitis [8% vs 1%]; anemia [7% vs 1%]; dyspnea [4% vs 1%]; hyperglycemia [5% vs <1%]).

Snapshot of Key Trial Resultsa

BOLERO-2 Placebo exemestane
(n = 239)
Everolimus exemestane
(n = 485)
Progression-free survivalb (median) 3.2 mo 7.4 mo
Clinical benefit ratec 25.5% 50.5%

CLEOPATRA Placebo trastuzumab docetaxel Pertuzumab trastuzumab docetaxel
Progression-free survival (median) 12.4 mo
(n = 406)
18.5 mo
(n = 402)

Objective response rate
Complete response rate
Partial response rate
(n = 336)
(n = 343)
aBased on data presented at 2011 CTRC-AACR San Antonio Breast Cancer Symposium.
bLocally assessed
cIncludes complete response, partial response, stable disease >6 months.

CLEOPATRA Data Endorse Adding Pertuzumab for Dual Blockade

The second major presentation concerned the results of the CLEOPATRA trial, a randomized placebocontrolled phase III study involving 808 HER2-positive patients with breast cancer who either received the combination of docetaxel plus trastuzumab or these 2 agents plus pertuzumab. 2,3 There was a rather striking improvement in the median time to disease progression (18.5 mo vs 12.4 mo; HR, 0.62; P <.0001) associated with treatment with the 3-drug “dual HER2 blockade” regimen compared with management with docetaxel and trastuzumab.

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