This article is more than 5 years old. Information may no longer be current.

Bevacizumab improved PFS in HER-2–positive breast cancer

Add topic to email alerts

Receive an email when new articles are posted on

Please provide your email address to receive an email when new articles are posted on .

Subscribe

Added to email alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

Back to Healio

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

Back to Healio

San Antonio Breast Cancer Symposium

SAN ANTONIO — Adding bevacizumab to conventional treatment of trastuzumab and docetaxel improved PFS in patients with HER-2–positive, locally recurrent or metastatic breast cancer, according to data presented here.

Luca Gianni, MD, director of medical oncology at the San Raffaele Cancer Center in Milano, Italy, said preclinical data and phase 2 data provide the rationale for combining trastuzumab (Herceptin, Genentech) and bevacizumab (Avastin, Genentech), but the AVEREL trial is the first randomized trial of the combination.

“HER-2–positive metastatic breast cancer has many therapeutic opportunities, but better medicines are needed,” Gianni said. “There is a strong preclinical rationale for combining trastuzumab and bevacizumab. VEGF expression is positively regulated by HER-2, and VEGF levels correlate with HER-2 overexpression. Also, trastuzumab and bevacizumab have synergy in vivo models.”

The study included 424 patients with HER-2–positive, locally recurrent or metastatic breast cancer who presented to 60 centers between September 2006 and February 2010. Patients had an ECOG performance status of 0 or 1, and they had received no prior chemotherapy for advanced disease. Patients with central nervous system metastases were excluded.

The patients were randomly assigned to trastuzumab and docetaxel or trastuzumab and docetaxel with bevacizumab. Trastuzumab and bevacizumab were assigned until disease progression, and docetaxel was assigned in a minimum of six cycles unless the disease progressed or there was unacceptable toxicity. The primary endpoint of the study was PFS, and additional endpoints included OS, response rate, duration of response, time to treatment failure, safety, quality of life and translational research.

Median follow-up was 26 months. The investigator assessment showed that patients who received bevacizumab had a PFS of 16.5 months vs. 13.7 months for those who did not receive it, which is an 18% reduction in the risk for progression or death. An independent review committee analysis showed a 28% reduction in the risk for progression or death with bevacizumab.

The grade-3 adverse effects that were more common in the group receiving bevacizumab included congestive heart failure, febrile neutropenia and hypertension.

Exploratory analyses of plasma VEGF-A suggest a potentially predictive effect, Gianni said. Those with higher plasma VEGF-A levels had a greater benefit with bevacizumab. According to Gianni, a global biomarker study of bevacizumab plus paclitaxel will stratify patients by plasma VEGF-A levels.

Disclosure: Dr. Gianni is a consultant for Roche, Genentech, GlaxoSmithKline, Wyeth, Novartis, Eisai, Pfizer, Millennium, Takeda, Sanofi-Aventis, Boehringer Ingelheim, Biogen Idec, AstraZeneca, Genomic Health and Celgene.

Earn CME this spring at the HemOnc Today Breast Cancer Review & Perspective meeting to be held March 23-24, 2012 at the Hilton San Diego Bayfront. See details at HemOncTodayBreastCancer.com.

The most exciting thing that may come out of this study is not the 2-3 month improvement in PFS, but the biomarker work that the researchers are undertaking to try to identify which patients will benefit from bevacizumab and which patients won't. We have very little evidence upon which to guide the selection of patients for use of bevacizumab in this setting, and unfortunately the average results of PFS across all patients are not as good as we'd like to see with a drug with the toxicity profile that bevacizumab has. Treating all patients with HER2-positive disease has seen a 2-3 month improvement in median PFS, but it's not a game changer at this point. This will convince many of us that it's still an active drug. But the reality is that there are patients who benefit and patients who do not. We've all seen very good and sometimes durable responses in our clinic since the drug became available, but it's only a subgroup of patients who benefit. At the moment, to identify responding patients, we are left with treating everybody, including a lot of patients who have little benefit. The key from this study and other studies is the fairly aggressive biomarker development underway. Researchers have been trying to do this for the best part of a decade. The antiangiogenisis agents, unlike some other agents, have been difficult to characterize in terms of the clinical profile or a genomic or molecular marker that will indicate that the patient will respond. Hopefully this study will provide basis upon which to move the field forward in the foreseeable future.

Gary Lyman, MD

Professor of Medicine, Division of Medical Oncology, Duke University

Disclosure: Dr. Lyman reports no relevant financial disclosures.

For more information:

• Gianni L. #S4-8. Presented at: 2011 CTRC-AACR San Antonio Breast Cancer Symposium; Dec. 6-11, 2011; San Antonio.

Follow HemOncToday.com on Twitter.