Remarkable Breakthrough for Metastatic Breast Cancer?

What You Need to Know: Got HER2 positive cancer that is metastatic? Final results from the CLEOPATRA study show that the combination of two targeted agents (with chemotherapy) significantly improves survival, compared to Herceptin (trastazumab) alone. This may be the biggest breakthrough ever for metastatic breast cancer, but only applies to those whose tumors overexpress HER2.

Background: HER2/neu (human epidermal growth factor receptor 2), also called ErbB2, is a protein that appears on the surface of some breast cancer cells. This protein is an important part of the pathway for cell growth and survival.

  • HER2/neu-positive (HER2+) breast cancers have a lot of HER2/neu protein.
  • HER2/neu-negative (HER2-) breast cancers have little or no HER2/neu protein.
  • About 15 to 20 percent of all breast cancers are HER2+ (you also may hear the term “HER2 over-expression”). HER2 status helps guide treatment.
  • HER2+ breast cancers can benefit from anti-HER2/neu drugs, such as the drug trastuzumab (Herceptin), which directly target the HER2/neu receptor. Trastuzumab and other anti-HER2/neu targeted therapies are not used for HER2- cancers.

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What We Just Learned: Final results from the CLEOPATRA study show that the combination of 2 targeted agents, trastuzumab (Herceptin, Roche/Genentech) and pertuzumab (Perjeta, Roche/Genentech), significantly prolonged survival in HER2-positive metastatic breast cancer, compared with trastuzumab alone. The targeted agents were added to chemotherapy with docetaxel.

Patients with metastatic breast cancer treated with the combination of Herceptin and Perjeta plus chemotherapy lived 15.7 months longer than those who received trastuzumab and chemotherapy (median overall survival, 56.5 vs. 40.8 months; hazard ratio [HR], 0.68; P = .0002).

“I think these results are phenomenal,” said Dr. Swain, who spoke during a press briefing here at the European Society for Medical Oncology (ESMO) Congress 2014. “We all believe that the 56.5-month median overall survival is unprecedented in this indication and confirms that the pertuzumab plus trastuzumab regimen is a first-line therapy for patients with HER2-positive metastatic breast cancer.”

She noted that the median survival with trastuzumab is already very good, at 40.8 months. “That already changed things for patients with HER2-positive breast cancer, but adding pertuzumab has increased that by 15.7 months,” Dr. Swain continued.    “I’ve never seen that in any other trial of metastatic breast cancer,” she said, noting that she has worked in the field for 30 years.

These final results add another 20 months of follow-up to the last presentation of the data, Dr. Swain said. The new results include an updated progression-free survival analysis, which was 18.7 months, an improvement of 6.3 months, compared with a median of 12.4 months with trastuzumab and chemotherapy alone. “This is also very good,” she said. “For those who are looking at different end points in this blinded study, progression-free survival was a good surrogate end point for overall survival.”

“We should consider this combination as the standard of care for our patients,” coauthor Javier Cortés, MD, director of the breast cancer program at Vall d’Hebron Institute of Oncology in Barcelona, Spain, said in a statement. “I can see no reason to justify the use of trastuzumab without pertuzumab.”

“What is more surprising is that the improvement in median overall survival exceeds the improvement in progression-free survival, maybe because of the different mechanisms of action that monoclonal antibodies have,” he explained.

My Take: This study is a peek into the future for most cancers: Cancer cells are driven by a particular pathway (in this case in the HER2 overexpression track), and we are at the very beginning of learning to target them. Kudos to Dennis Slayman, MD for kicking open the HER2 door. We need more such breakthroughs by stubborn courageous big thinkers. Want to hear the thrilling story of the development of the breakthrough drug Herceptin (trastazumab)? Head to (, or better yet, order from your local bookseller. I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.


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Harvard AB Yale MD UPenn Radiation Oncology Radiation Oncologist, Seattle area

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