Breast Oncologists Incorporate New Treatments, Grapple With Ongoing Challenges

Beth Fand Incollingo @fandincollingo
Published: Friday, Oct 05, 2012
Dr. Hope Rugo

Hope Rugo, MD

During the 11th International Congress on The Future of Breast Cancer, Hope Rugo, MD, offered a snapshot of the research community’s progress in the study and treatment of the disease.

In two presentations, Rugo, clinical professor and director of the Breast Oncology Trials Program at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, addressed the elusive promise of angiogenesis inhibitors in metastatic breast cancer, as well as new strategies for treating estrogen-positive metastatic disease.

In addition, Rugo sat down with Oncology & Biotech News to discuss those topics and others, including key developments in the treatment of HER2-positive breast cancer—in particular, the FDA’s recent approval of pertuzumab.

The exchange includes advice on how the newest drugs, techniques for matching patients with treatments, and insights into the cancer genome can be incorporated into community oncology practice.

OBTN: On June 8, the FDA approved pertuzumab, in combination with trastuzumab and docetaxel, for the treatment of metastatic HER2-positive breast cancer. How will this change the treatment paradigm for patients with this disease, and what should oncologists know about using it?

Dr Rugo: Prior to the approval of pertuzumab, our standard was trastuzumab combined with chemotherapy, or in patients who had progressed on a trastuzumab-based regimen in the adjuvant setting within 6 to 12 months, lapatinib and capecitabine.

The approval of pertuzumab has set a new standard of care, which is treating patients in the first-line metastatic setting with trastuzumab, pertuzumab, and a taxane—either docetaxel or paclitaxel.

Thankfully, when we added pertuzumab to trastuzumab, we saw very little additional toxicity—a bit more diarrhea. It’s something to tell your patients so they can take Imodium if they need to. Also, there was no additional cardiac toxicity when we added pertuzumab to trastuzumab, suggesting that the screening we do now is appropriate in patients who have minimal exposure to prior cardiotoxins.

As far as how to apply this in practice, the question is, “Should we use this regimen for everybody in the first-line setting, regardless of how they present?”

And I think that’s hard to answer. There was an early survival benefit in the initial data from the CLEOPATRA trial [N Engl J Med. 2012;366:109-119], so in a patient who has HER2-positive metastatic breast cancer in the first-line setting, I’d go with that. After a good response, I would drop the chemotherapy and continue the two antibodies alone.

Where patients have received adjuvant or neoadjuvant chemotherapy that includes a taxane and then developed metastatic disease, their chances of responding to another taxane or the same taxane is small. But for most patients who relapse after completing their year of trastuzumab, I think that a taxane, trastuzumab, and pertuzumab is still a very reasonable initial regimen to see if we can overcome some degree of resistance.

So what happens to a patient who’s gotten trastuzumab, pertuzumab, and a taxane and then developed progressive disease? I would caution against continuing pertuzumab after progression, because we have no data that it would be beneficial, and it would be very costly. We do know that other HER2-directed therapies may be active in that setting, so when T-DM1 [trastuzumab emtansine] is approved, I would have no hesitancy in giving that agent, and certainly lapatinib and lapatinib combinations, like lapatinib/ trastuzumab, may be active in that setting, as well.

What other investigational agents are in the pipeline for the treatment of HER2-positive disease?
T-DM1 is the next drug that will be approved for the treatment of HER2-positive breast cancer. It’s a novel agent and the first in its class in breast cancer to combine the antibody qualities of trastuzumab and a very potent microtubule toxin derivative of emtansine with a stable linker, so that you can direct the chemotherapy agent directly to the cancer cell.

The EMILIA trial (J Clin Oncol. 2012;30[suppl; abstr LBA1]) demonstrated a marked improvement in progression- free survival [PFS] and response when it compared T-DM1 to lapatinib and capecitabine, and with different, but overall reduced, toxicity. With lapatinib, you see the diarrhea, hand-foot syndrome, and rash, and it involves taking a bunch of pills. With T-DM1, patients just came in every 3 weeks and got an intravenous infusion with a very small amount of GI side effects.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: 16th Annual International Congress on the Future of Breast Cancer®Sep 29, 20182.0
School of Breast Oncology®: Mid-Year Video Update OnlineSep 30, 20182.0
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