The CLEOPATRA and BOLERO-2 Studies are Stirring Excitement at SABCS

The results of 2 studies likely to have a significant impact upon the treatment of women with metastatic breast cancer.


The results of 2 studies likely to have a significant impact upon the treatment of women with metastatic breast cancer were released Wednesday evening at the CTRC-AACR San Antonio Breast Cancer Symposium, generating optimism about the potential for dramatic strides in 2 types of the disease.

Both studies will be discussed in press briefings and panel sessions as the symposium unfolds this week at the Henry B. Gonzalez Convention Center. Here is an advance summary of the research:

Pertuzumab Significantly Improves PFS

Findings from the CLEOPATRA trial indicate that combining pertuzumab with trastuzumab (Herceptin) and docetaxel chemotherapy reduced the risk of progression by 38% in women with metastatic HER2-positive disease.

The international, double-blind, phase III trial involved 808 women randomly assigned to receive a regimen in which pertuzumab was added to trastuzumab and docetaxel, versus placebo plus trastuzumab and docetaxel.

José Baselga, MD, PhD

José Baselga, MD, PhD

Those who received pertuzumab, which included 402 patients, experienced a median progression-free survival (PFS) of 18.5 months, compared with a median PFS of 12.4 months among the 406 patients in the placebo group (hazard ratio = 0.62; P = <0.0001). In addition, the objective response rate (tumor shrinkage ≥30%) was 80.2% in the pertuzumab group as opposed to 69.3% in the placebo arm.

“Most metastatic patients with HER2-positive breast cancer eventually stop responding to trastuzumab, so the fact that we now have an agent that can be added to current treatment to delay progression is very exciting,” said José Baselga, MD, PhD, a professor in the Department of Medicine at Harvard Medical School and chief of Hematology/Oncology at Massachusetts General Hospital in Boston, in an SABCS press release. He is the senior researcher on the trial.

The regimen employs a dual HER2 inhibition strategy. Trastuzumab targets HER2, while pertuzumab is the first in a new class of HER2 dimerization inhibitors that prevents HER2 receptor proteins from linking to other HER receptors, according to Genentech, which is developing the drug.

Genentech, a San Francisco-based company that is a member of the Roche Group, said an application has been submitted with the FDA for pertuzumab to be used for patients with previously untreated HER2-positive metastatic breast cancer. (Abstract S5-5)

Evidence Mounts for Everolimus Benefits

Longer-term data from the BOLERO-2 trial continue to demonstrate that combining everolimus (Afinitor) with exemestane significantly enhances PFS for postmenopausal women with estrogen receptor-positive metastatic disease.

The phase III, double-blind trial included 724 patients who had experienced disease progression after receiving previous endocrine therapy consisting of either anastrozole or letrozole, in treatment plans that variously included tamoxifen, fulvestrant, and chemotherapy. Participants were randomized 2:1 to receive either everolimus plus exemestane or exemestane alone with a placebo.

The latest data indicate a median PFS of 7.4 months for the 485 patients treated with the everolimus combination versus a median PFS of 3.2 months for the 239 patients in the placebo group.

Gabriel N. Hortobagyi, MD

Gabriel N. Hortobagyi, MD

In addition, patients treated with the everolimus regimen experienced a 50.5% clinical benefit rate as opposed to 25.5% for those in the placebo arm. The benefit rate combines complete response, partial response, or stable disease >6 months.

“These results establish a new standard of care for this group of patients,” said Gabriel N. Hortobagyi, MD, chair of the Department of Breast Medical Oncology and director of the Multidisciplinary Breast Cancer Research Program at the University of Texas MD Anderson Cancer Center in Houston, in an SABCS press release. He is the lead researcher.

Afinitor, an inhibitor of the mTOR pathway, is FDA-approved for the treatment of advanced renal cell carcinoma, subependymal giant cell astrocytoma associated with tuberous sclerosis, and progressive neuroendocrine tumors of the pancreas.

Novartis Pharmaceuticals Corporation, which is based in East Hanover, New Jersey, said it plans to file regulatory submissions with the FDA based on the BOLERO-2 results by the end of this year. (Abstract S3-7)

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