Metastatic Breast Cancer News from the 2011 San Antonio Breast Cancer Symposium

Today we'll continue to cover headlines from the 2011 San Antonio Breast Cancer Symposium, with a focus on six studies relevant to women with metastatic breast cancer.

Links may be found on the treatment pages of our LATESTBreastCancer.com website.

Omnitarg for HER2 positive metastatic breast cancer

The phase III Omnitarg (pertuzumab) study, known as CLEOPATRA (CLinical Evaluation Of Pertuzumab and TRAstuzumab), was big news. Reuters, Medical News Today, The New York Times and Los Angeles Times all ran stories. The study was published in the New England Journal of Medicine on December 7. (Link to full text.)

In the study, 808 women with HER2 positive metastatic breast cancer were randomly assigned to receive Herceptin (trastuzumab) and Taxotere (docetaxel) either with or without Omnitarg.

For the Omnitarg group, median progression-free survival, meaning the amount of time the cancer remains stable, was 18.5 months compared to 12.4 months for the Herceptin/Taxotere only group.

Although it's too early to confirm overall survival data, preliminary results show 69 deaths among the 402 women treated with Omnitarg compared to 96 deaths among the 406 women who did not receive Omnitarg.

Genentech and its parent company, Roche, have applied for permission to market Omnitarg in the US and Europe as first-line treatment for HER2 positive metastatic breast cancer.

Avastin for HER2 positive metastatic breast cancer

After the recent FDA decision to pull approval of Avastin for metastatic patients, there has been interest in identifying subsets of patients who may benefit from Avastin.

The phase III study (AVEREL) of Avastin (bevacizumab) in HER2 positive metastatic patients was similar in design to the Omnitarg study. 208 women were treated with Herceptin and Taxotere alone. 216 also received Avastin. The New York Times, Los Angeles Times and US News and World Report/HealthDay covered the study.

For the Avastin group, progression-free survival was 16.5 months, compared to 13.7 months for the 208 in the Herceptin/Taxotere only group.

But some question whether small benefits in progression-free survival are important.

According to the New York Times, "there was absolutely no difference in how long the women lived." Genentech has decided not to apply for FDA approval for HER2 positive breast cancer. A company representative noted, "Our bottom line is we do not believe that the difference in P.F.S. is of a sufficient magnitude that it is likely to gain regulatory approval."

Future research will attempt to identify the subset of patients who benefit from Avastin. As Dr. Gabriel Hortobagyi from MD Anderson noted in Los Angeles Times,

"I have no doubt that Avastin is a very powerful drug for some patients. . . The problem with Avastin is we don’t have a biomarker to help us identify the sub-group."

Afinitor for hormone-receptor positive metastatic breast cancer

A study (BOLERO-2) of Afinitor (everolimus) involving 704 women with hormone-receptor positive breast cancer which progressed on prior hormone therapy was covered by The New York Times, Los Angeles Times and Medical News Today. The study was published in The New England Journal of Medicine on December 7. (Link to full text.)

For women who took Afinitor plus the aromatase inhibitor Aromasin (exemestane), median progression-free survival was 7.4 months, compared to 3.2 months for women who took Aromasin alone.

However, the New York Times (Dec. 7) noted that because all women had already failed to benefit from hormone therapy, "perhaps it is not surprising that the control arm did not do that well on exemestane alone."

But, the trial researchers said that doctors often prescribe Aromasin in practice when other hormone therapies fail.

Medical News Today quoted Dr. Hortobagyi, a study coauthor, to say, "These findings may establish a new standard of care for advanced breast cancer."

Faslodex for hormone-receptor positive metastatic breast cancer

A phase III trial (SWOG S0226) of Faslodex (fulvestrant) plus Arimidex (anastrozole) for women with hormone-receptor positive metastatic breast cancer was covered by the Medical News Today on December 9.

In the study, 707 postmenopausal women were assigned to receive Arimidex plus Faslodex or Arimidex alone. Compared to the Arimidex alone arm, the Faslodex arm experienced longer median overall survival (47.7 months vs. 41.3 months) and longer progression-free survival (15 months vs. 13.5 months).

Both Arimidex and Faslodex are already used to treat breast cancer, though not in comination. The lead study coordinator noted that "these patients have not had a new treatment that gave them an overall survival benefit in more than a decade."

Entinostat for hormone-receptor positive metastatic breast cancer

A small phase II study (ENCORE 301) of entinostat for locally recurrent or metatstatic breast cancer was covered in a PR Newswire press release and the New York Times (Dec. 7)

In the study, 130 patients were treated with Aromasin (exemestane) alone or Aromasin plus entinostat. The median overall survival for the entinostat group was 26.9 months, compared to 19.8 months in the Aromasin alone group. Progression-free survival was also better with entinostat (4.3 months vs. 2.3 months.)

A randomized phase III study is anticipated to begin enrollment in the first half of 2012.

Abraxane as first-line treatment for metastatic breast cancer

A phase II study comparing Abraxane (nab-paclitaxel) to Taxotere (docetaxel) as first-line therapy for metastatic breast cancer was covered by Medical News Today on December 12.

In the study, 300 women who received no prior chemotherapy for metastatic disease were divided into four groups. Three groups received different doses of Abraxane. The fourth group received Taxotere.

The best median overall survival was achieved by the group that received 150 mg of Abraxane twice weekly (33.8 months.) The other two Abraxane dose schedules achieved median overall survival of 22.2 months and 27.7 months. For the Taxotere group, median overall survival was 26.6 months.

Progression-free survival was also better for the Abraxane 150mg/twice weekly group at 14.6 months, compared to 7.5 months and 10.9 months for the other Abraxane doses and 7.8 months for the Taxotere group.


We'll continue to follow research developments for women with metastatic breast cancer. We add links to media stories and journal abstracts to our website, LATESTBreastCancer.com everyday. The latest news and research may be explored anytime by clicking the Treatments tab.

The Breast Cancer News Update: July 18

This weekend, Omnitarg (pertuzumab), a monoclonal antibody for the treatment of HER2 positive breast cancer, made news as positive phase III study results were announced. Today we'll highlight the latest news and research on Omnitarg for HER2 positive breast cancer. All of the news articles, reviews and studies discussed below can be found on the Omnitarg (pertuzumab) page of the LATESTBreastCancer.com website.

Omnitarg: A little background and biology

For HER2 positive breast cancer, Herceptin (trastuzumab) has been the treatment of choice. Unfortunately, some HER2 positive breast cancers do not respond to Hercpetin and some develop a resistance to Herceptin over time. This has led to the development of new targeted drugs for HER2 positive breast cancer. A 2011 review in Swiss Medical Weekly overviewed the development of Herceptin and Omnitarg (as well as Tykerb (lapatinib), Trastuzumab DM-1, and Rexomun (Ertumaxomab)) for HER2 positive breast cancer. The full-text of the review is available free of charge, which is not always the case with journal reviews.

How does Omnitarg work? A short YouTube video posted by BusinessWire explains the biology behind Omnitarg. Basically, Omnitarg blocks the pairing (or dimerizing) of HER2 proteins with other HER proteins (HER1, HER2, HER3 and HER4). This is different than Herceptin, which attaches to HER2 receptors and blocks them from receiving growth signals. (See the Breastcancer.org summary for more on how Herceptin works.)

Omnitarg: The latest research

Positive phase III study of Omnitarg plus Herceptin and Taxotere

On Friday, Reuters and Medical News Today published articles covering the announcement of positive phase III trial results of Omnitarg plus Hercpetin and Taxotere (docetaxel) for metastatic breast cancer. Progression free survival was longer for those treated with all three drugs than for those treated with Herceptin and Taxotere alone. The study results are expected to be submitted for global regulatory approval later this year.

Recent cardiac safety study

One of the concerns with Herceptin is the risk of cardiac side-effects. Omnitarg may not raise the same concerns. A June 2011 study published in the Annals of Oncology concluded that patients treated with Omnitarg experienced "relatively low levels" of asymptomatic left ventricular systolic dysfunction (LVSD) and symptomatic heart failure (HF). "There was no notable increase in cardiac side-effects when pertuzumab was given in combination with other anticancer agents," such as Herceptin or non-anthracycline based chemotherapies, such as Taxotere.

Omnitarg: Other studies

Phase II studies for metastatic cancer

In March 2010, two phase II studies of Omnitarg for metastatic breast cancer were published in the Journal of Clinical Oncology . One from Spain found that the combination of Omnitarg and Hercpetin was "active and well tolerated in patients with metastatic HER2-positive breast cancer who had experienced progression during prior trastuzumab therapy." Both the Journal of Clinical Oncology abstract and a February 2010 Cure Today story can be found on the Omnitarg page of our website. The other study, from Italy, concluded that Omnitarg was not effective as a single agent in treating HER2 negative metastatic breast cancer.

Neoadjuvant studies

Omnitarg is not just being studied for metastatic breast cancer. In December 2010, Cure Today and Medical News Today reviewed the positive phase II study of Omnitarg plus Herceptin and Taxotere in the neoadjuvant (before surgery) setting for women with newly diagnosed breast cancer. A November 2010 review in Cancer Treatment Reviews also addressed the research on neoadjuvant Omnitarg.

Other research and reviews

In addition to the studies discussed above, the LATESTBreastCancer.com Omnitarg page contains links to research at the cellular level (December 2009 and February 2011 Cancer Research studies) and several comprehensive reviews of the development of Omnitarg for HER2 positive breast cancer.

We'll continue to monitor Omnitarg developments and add the latest news and research to our website and database. As always, our goal is to monitor and organize breast cancer research for you.

HER2 Part 3: Drugs that Target HER2

Note: This is the blog of LATESTBreastCancer.com, where you can get personalized information about the latest in breast cancer treatment.

For patients with HER2 over-expressing breast cancer, it is critical to target the HER protein. Here we'll look at an array of HER2 targeted drugs: current, new and future. If you're a patient with metastatic disease whose disease is progressing following Herceptin treatment, accessing one of these newer drugs through a clinical trial might be a reasonable option.

Herceptin (trastuzumab). "The big standard." The first drug to target HER2. Approved in 1998. Currently used for patients with all stages of HER2+ breast cancer. Picture how it works: Herceptin is a very large monoclonal antibody protein. It attaches to HER2 on the portion of the molecule that sits outside the cell. By binding to it, Herceptin effectively "flags" the cancer cell for destruction by the body's own immune system. Herceptin also seems to inhibit HER2 growth signaling more conventionally. But attracting an immune system attack is the primary way the drug works (also called, by pharma nerds, "mechanism of action" or MOA).

Tykerb (lapatinib). "The little newcomer." The second HER2 drug. Unlike Herceptin, Tykerb is a very small molecule that inhibits not only HER2 but also EGFR (HER1). Also unlike Herceptin, Tykerb attaches to EGFR and HER2 inside the cell. HER2 and EGFR still pair up with other members of the HER family, but because of Tykerb binding, the grow signal is never sent to other molecules in the "relay chain." Tykerb is used in patients with metastatic disease if they progress after using Herceptin. The other key point about Tykerb is that because it is a very small molecule, it can travel from the bloodstream into the brain, and it seems to reduce brain metastases in HER2 positive patients.

T-DM1. "Targeted AND chemotherapy." A modified version of Herceptin (trastuzumab). In this case "T" (trastuzumab) is attached to another molecule called "DM1" which is a traditional chemotherapeutic. How about this for tricky: the trastuzumab portion of the drug attaches to HER2 outside the cell. When it does, it causes HER2 to get pulled inside the cell, where there (and only there) the chemotherapy portion of the drug is released and kills the cell. So the chemotherapy only kills HER2-laden cancer cells and isn't released where it could do damage to other cells. T-DM1 appears to be doing well in clinical trials and is generating excitement.

OmniTarg (pertuzumab). "Separate, you two!" Remember that to send the grow signal inside the cell, HER family molecules on the cell membrane have to pair up. Well, Genentech has created a drug that inhibits this pairing ("dimerization"). Pertuzumab is a large monoclonal antibody like Herceptin. Like Herceptin, it binds to HER2 outside the cell. But it binds to a different part of the molecule than Herceptin, effectively inhibiting HER2 from pairing up with EGFR (HER1), HER3 and probably HER2 as well. No pairing, no growth signal. Lone HER2s just float around the cell membrane doing nothing. Cancer cell growth and proliferation slows or halts (in theory).

afatinib and neratinib "Same but (maybe) better." These two drugs are in clinical trials. They both work much like Tykerb, but they might end up being more potent and thus more effective. Like Tykerb, both are small molecules, both are taken orally as tablets, and both attach to HER2 inside the cell to inhibit growth signaling. But unlike Tykerb, they are so-called "irreversible" inhibitors of HER2. They bind and then stay attached to HER2. Tykerb is a "reversible" inhibitor that binds but sometimes detaches.

To find clinical trials for these drugs, you can go to clinicaltrials.gov. Or, better yet, try out a newer, easier-to-use site called BCTrials.org. This site provides personalized info about available clinical trials. It's sponsored by UC San Francisco.

Next: How doctors determine if you're HER2 positive