Pertuzumab Data Highlight Potential of Triplet Regimens in MBC

Published: Wednesday, Oct 08, 2014


Treating Advanced Breast Cancer in Community Settings


Adam M. Brufsky, MD, PhD
Professor, Medicine
University of Pittsburgh
Associate Division Chief, Hematology/Oncology
Co-Director, Comprehensive Breast Cancer Center
Pittsburgh, PA


Sara A. Hurvitz, MD
Associate Professor, Medicine
Ronald Reagan UCLA Medical Center
UCLA Health
Los Angeles, CA

Eleftherios P. Mamounas, MD
Professor, Surgery
University of Florida Health Cancer Center
Orlando, FL

Hope S. Rugo, MD
Professor, Medicine
Breast Director, Breast Oncology Clinical Trials Education
University of California, San Francisco
Helen Diller Family Comprehensive Cancer Center
San Francisco, CA

Dia Voudouris, MD
Clinical Associate Professor, Medicine
Manhattan Cancer Specialists
Mount Sinai School of Medicine
Lenox Hill Hospital
New York, NY
New therapeutic strategies utilizing triplet regimens for the treatment of patients with HER2-positive metastatic breast cancer (MBC) continue to emerge as an exciting area of development, according to a panel of experts who participated in a recent OncLive Peer Exchange.®

Fresh clinical trial findings have bolstered the role of pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) and chemotherapy as a first-line standard of care for this patient population,1 yet clinicians already were widely employing this regimen based on earlier data.2

Meanwhile, the combination of pertuzumab with trastuzumab and hormonal therapy has generated excitement as a potential option for patients with HER2-positive and estrogen receptor (ER)–positive breast cancer, and represents an area for future research, the panelists said during a wide-ranging discussion entitled “Treating Advanced Breast Cancer in Community Settings.”

CLEOPATRA Solidifies Pertuzumab Regimen

Adam M. Brufsky, MD, PhD, who served as moderator of the Peer Exchange program, called the development of pertuzumab in both early and metastatic disease “one of the big success stories in the treatment of breast cancer” in the past 20 years.

The FDA initially approved pertuzumab in combination with trastuzumab and docetaxel as a frontline treatment for patients with HER2-positive tumors in 2012, based on findings from the phase III CLEOPATRA trial. This indication was followed by the approval of pertuzumab, trastuzumab, and chemotherapy as a neoadjuvant therapy for early-stage HER2-positive breast cancer in 2013.

Dr. Adam Brufsky

Adam Brufsky, MD

In September, long-term follow-up results from the CLEOPATRA trial were among the big stories to emerge from the 2014 ESMO Congress in Madrid, Spain. Swain et al reported that dual anti-HER2 blockade with pertuzumab and trastuzumab plus chemotherapy improved median overall survival (OS) by 15.7 months over standard first-line therapy.1

The triplet combination extended median OS to 56.5 months without introducing any new safety concerns. The data were from the final OS analysis after a median follow-up of 50 months. Adding pertuzumab to the regimen yielded a hazard ratio of 0.68 (P = .0002) compared with standard first-line treatment.

In the CLEOPATRA trial, 808 women were randomized to receive either first-line trastuzumab, docetaxel, and pertuzumab (n = 402) or trastuzumab, docetaxel, and placebo (n = 406). The primary endpoint was progression-free survival (PFS), with secondary outcome measures focused on OS and response.

Patients received either placebo or pertuzumab, given as an 840-mg loading dose followed by a 420-mg maintenance dose, plus trastuzumab, given as an 8-mg/kg loading dose followed by a 6-mg/kg maintenance dose, and 6 cycles of docetaxel, 75 mg/m2 with escalation to 100 mg/m2 if tolerated. Treatments were administered every 3 weeks and continued until disease progression.

In the primary analysis, the median PFS was 18.5 months versus 12.4 months in the pertuzumab and placebo arms, respectively (HR = 0.62; P <.0001).2 The objective response rate was 80.2% in the pertuzumab arm compared with 69.3% with placebo. The median duration of response was 20.2 versus 12.5 months, for the pertuzumab and placebo arms, respectively.

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