Early results from the very small, very early study reviewed here suggests that some advanced-stage, HER2-positive breast cancers that have stopped responding to Herceptin (chemical name: trastuzumab) may respond to one of two experimental treatments:
The results were presented at the 2010 American Society of Clinical Oncology (ASCO) annual meeting.
Herceptin is used to treat advanced-stage, HER2-positive breast cancer 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 (DM1), like some other chemotherapy medicines, disrupts the way cells grow. Maytansine on its own isn't considered a targeted therapy, which means it can affect healthy cells as well as cancer cells. T-DM1 was designed to deliver maytansine to cancer cells in a targeted way by attaching the maytansine to the Herceptin. Herceptin then carries the maytansine only to the cancer cells.
Like Herceptin, Omnitarg works by stopping the HER2 protein from telling cancer cells to grow.
In the on-going study reviewed here, 43 women and one man diagnosed with advanced-stage, HER2-positive breast cancer that had stopped responding to Herceptin were treated with either T-DMI alone or T-DM1 with Omnitarg. These early results are from 28 women in the study.
Of those 28 women, 23 (82%) got some benefit from T-DM1 and Omnitarg:
Four women had the cancer grow while being treated with T-DM1 and Omnitarg.
One women stopped taking T-DM1 and Omnitarg because of heart problems. One other woman died of pneumonia that seemed to be related to the cancer growing and not related to treatment. Herceptin and Omnitarg can cause serious side effects, including heart and lung problems.
It's important to know that T-DM1 and Omnitarg are not currently approved by the U.S. Food and Drug Administration to treat breast cancer.
The study reviewed here is a phase I study. In phase I studies, researchers are figuring out the best way to give a new treatment, as well as the highest dose that can be given safely, without serious side effects. Phase I studies also help researchers figure out if a larger study involving more people makes sense.
Based on these promising results, doctors will continue to study the potential benefits of using T-DM1 and Omnitarg to treat breast and other cancers.
If you're being treated for advanced-stage, HER2-positive 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 experimental treatments such as T-DM1 and Omnitarg. 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.
CHICAGO (MedPage Today) -- A small phase I clinical trial suggests that trastuzumab (Herceptin) conjugated to DM-1 (T-DM1) with or without pertuzumab has some effectiveness for women with advanced HER2-positive breast cancers previously treated with trastuzumab, researchers said here.
Although the results are preliminary from a study focused on dosing and toxicity, 10 of 28 participants achieved partial responses, about 35.7%, when treated with T-DM1 and pertuzumab, said Kathy Miller, MD, associate professor of medicine at the Indiana University Melvin and Bren Simon Cancer Center, Indianapolis. Another 13 patients achieved disease stabilization, meaning a clinical benefit of treatment was seen in 82.1% of the participants in this study, Miller said at the 2010 annual meeting of the American Society of Clinical Oncology.
T-DM1 is a HER2-targeted antibody drug-conjugate composed of the cytotoxic agent DM1 (an antimicrotubule agent) conjugated to the monoclonal antibody trastuzumab. Pertuzumab is a humanized monoclonal antibody that binds to a different HER2 receptor than T-DM1.
"The theory with using these agents is that we can more fully cover the HER receptors," Miller told MedPage Today. "The combination of pertuzumab and trastuzumab or T-DM1 provides a complementary mode of action that may be efficacious for treatment of HER2-overexpressing diseases."
The study has so far enrolled 44 patients with locally advanced or metastatic HER2-positive breast cancers -- including one male breast cancer patient. Miller reported on preliminary outcomes for 28 of the participants. The average age of the patients was 55; about 90% were white. All had received previous trastuzumab therapy as well as other forms of chemotherapy.
"T-DM1 at a dose of 3.6 mg/kg plus full dose pertuzumab (840 mg loading dose and then 420 mg) has an encouraging safety and tolerability profile," Miller said. "Thrombocytopenia and hepatic transaminase elevations generally were transient, reversible, and did not occur at a higher rate than that observed with T-DM1 alone."
Among the 28 patients for whom results were reported, four experienced disease progression, and one patient discontinued both drugs after developing ventricular dysfunction. One patient died of pneumonia, apparently due to disease progression. However, the investigators did not believe her death was due to the combination treatment.
"The use of two targeted agents in these advanced breast cancer patients is a reasonable approach to therapy," said Edith Perez, MD, the Serene M. and Frances C. Durling Professor of Medicine at the Mayo Clinic, Jacksonville, Fla.
The clinical trial was sponsored by Genentech and Roche.
Miller and co-authors disclosed financial relationships with Genentech, Roche, GlaxoSmithKline, Novartis, Pfizer, Roche, and Wyeth.
Perez has disclosed financial relationships with Bristol-Myers Squibb, sanofi-aventis, Pharmacia, and Genentech.
Primary source: Journal of Clinical Oncology Source reference: Miller K, et al "A phase Ib/II trial of trastuzumab-DM1 (T-DM1) with pertuzumab (P) for women with HER2-positive, locally advanced or metastatic breast cancer (BC) who were previously treated with trastuzumab (T)" J Clin Oncol 2010; 28(18S): 117s.
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