The study reviewed here found that some metastatic breast cancers that had stopped responding to many treatments did respond to an experimental treatment that's a combination of Herceptin (chemical name: trastuzumab) and a chemotherapy medicine called maytansine. These results were presented at the 2009 San Antonio Breast Cancer Symposium.
Herceptin is a targeted therapy medicine already approved by the U.S. Food and Drug Administration to treat advanced-stage, HER2-positive breast cancers and to lower the risk of recurrence of early-stage, HER2-positive breast cancer with a high risk of recurrence. HER2-positive cancers make too much of the HER2 protein. The HER2 protein sits on the surface of cancer cells and receives signals that tell the cancer to grow and spread. About one out of every four breast cancers is HER2-positive. Herceptin works by attaching to the HER2 protein and blocking it from receiving growth signals.
Maytansine, like some other chemotherapy medicines, disrupts the way cells grow. Maytansine isn't considered a targeted medicine, which means it can affect healthy cells as well as cancer cells.
The 110 women in this study had received a number of treatments for metastatic breast cancer but the cancer either didn't respond or stopped responding to the treatments. Many of the women already had been given Herceptin and Tykerb (chemical name: lapatinib), another targeted therapy medicine for HER2-positive cancers. Most of the cancers were HER2-positive.
The women were given the experimental combination of Herceptin and maytansine, known as T-DM1. T-DM1 was designed to deliver the chemotherapy medicine to cancer cells in a targeted way by attaching the chemotherapy medicine to the Herceptin. Herceptin then carries the chemotherapy medicine to the cancer cells.
Even though the women in the study already had been treated with a number of other medicines (heavily pretreated), some did respond to T-DM1.
Nearly half (44.5%) the women either stayed stable or improved for 28 days or more (called clinical benefit). This clinical benefit lasted from 1.2 to 8.4 months.
Less than 25% of the women had serious side effects. Most of the serious side effects were related to the chemotherapy part of the treatment and 5.5% of the women stopped treatment because of side effects. Herceptin can cause heart damage and can lead to heart failure. Only two women in this study had some decrease in heart function, but they didn't have heart failure.
These results are encouraging, especially since the cancers had stopped responding to so many other treatments. It's also interesting that Herceptin seemed to be effective against HER2-negative cancers; Herceptin is thought to work on only HER2-positive breast cancer. Still, this is a very small, early study on an experimental medicine. More research is needed before doctors understand the benefits and risks of this treatment.
If you're being treated for advanced-stage breast cancer, you and your doctor may be considering a number of treatment options, especially if the cancer has stopped responding to standard treatments. If you're willing to participate in a clinical trial, you may have even more options available, possibly including an experimental treatment such as T-DM1. Talk to your doctor about clinical trials that might be a good fit for you and your unique situation. Visit the Breastcancer.org Clinical Trials pages for more information.
And stay tuned to Breastcancer.org to learn about the latest research on new, better ways to treat breast cancer.
SAN ANTONIO (MedPage Today) -- A novel form of trastuzumab (Herceptin) with a chemotherapy-like conjugate attached appears to substantially improve outcomes in heavily-pretreated metastatic breast cancer, researchers said.
Median progression-free survival was 7.3 months (range 0.0 to 11.7) with single agent trastuzumab-DM1 (T-DM1) in a Phase II study reported here at the San Antonio Breast Cancer Symposium.
The objective response rate was 32.7% in women whose tumors had progressed after treatment with an anthracycline, taxane, capecitabine (Xeloda), trastuzumab, and lapatinib (Tykerb), including two HER2-targeted agents in the metastatic setting.
Moreover, the investigational agent was well tolerated, with no dose-limiting cardiotoxicity, according to Ian Krop, MD, PhD, of the Dana-Farber Cancer Center in Boston, and colleagues.
A response this good didn't even seem possible in a setting where women had received an average of seven prior agents, José Baselga, MD, of the Vall d'Hebron University Hospital in Barcelona, Spain, commented at the poster discussion session he moderated.
The new molecule consists of the trastuzumab monoclonal antibody, chemically fused to a cytotoxin: a potent microtubule inhibitor called maytansine that's derived from a sea sponge.
"It is supposed to pack the antibody, which targets the pathway, and the chemotherapy, which targets the cancer cell, hopefully as a smart missile that will target the cancer cell with minimal toxicity," explained Mothaffar Rimawi, MD, of Baylor College of Medicine in Houston, who wasn't involved in the study.
The agent is being developed by Genentech in partnership with ImmunoGen as a possible "replacement" for Genentech's trastuzumab, which comes off patent in 2015.
"Many people feel the data is worth bringing to the FDA, even though it is only Phase II, because these patients have no other options," Knop said standing at his poster.
The companies have given no specifics on filing but hinted in an investigator conference call that "clearly there is potential for filing and approval over the next 12 months for T-DM1." The drug is going into Phase III study for first-line treatment around May 2010.
Regardless, the early results presented here at SABCS generated a buzz at the meeting.
"It is just remarkable in Phase II activity against HER2-positive breast cancer that's resistant to trastuzumab and lapatinib," commented targeted therapy pioneer Mark Pegram, MD, of the University of Miami.
The study included 110 women assigned to open-label treatment with single agent trastuzumab-DM1 (3.6 mg/kg intravenously every three weeks).
Objective response rate as judged by an independent review board -- the primary endpoint -- was 32.7%, all partial responses. The duration ranged from 1.2 to 8.4 months.
Clinical benefit rate -- stable disease or complete or partial response maintained for at least 28 days -- was 44.5% as judged by the same outside experts.
For the 83.5% of patients confirmed to have HER2-positive disease, the objective response rate was even better (39.5%), as was the clinical benefit rate (52.6%).
The researchers reported no new safety signals with the drug, with observed toxicities called "acceptable and manageable."
Overall, 22.7% of patients had a serious adverse event -- most frequently fever, cellulitis, or pneumonia -- and 5.5% discontinued because of an adverse event.
Two patients had a drop in left ventricular ejection fraction of 15% to 24% but none dropped to a level that would be considered heart failure.
The study was supported by Genetech and F. Hoffman-LaRoche.
Study authors reported conflicts of interest with Genentech, including employment with Genentech, as well conflicts of interest with Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly, Amgen, Array Biopharma, Ariad, AstraZeneca, Exelixis, Merck, Takeda, Geron, and Pfizer.
Baselga reported conflicts of interest with Exelixis, Novartis, Merck, Roche, and GlaxoSmithKline.
Rimawi reported conflicts of interest with GlaxoSmithKline, Genentech, Pfizer, Novartis, and Abraxis.
Pegram reported potential conflicts of interest with Genetech, GlaxoSmithKline, sanofi-aventis, and Amgen.
Primary source: San Antonio Breast Cancer Symposium Source reference: Krop I, et al "A phase II study of trastuzumab-DM1 (T-DM1), a novel HER2 antibody-drug conjugate, in patients with HER2+ metastatic breast cancer who were previously treated with an anthracycline, a taxane, capecitabine, lapatinib, and trastuzumab" SABCS 2009; Abstract 710.
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