This small, early study suggests that Afinitor (chemical name: everolimus), a targeted therapy medicine, can make HER2-positive, metastatic breast cancers that have stopped responding to Herceptin (chemical name: trastuzumab) and Taxol (chemical name: paclitaxel) start responding to those treatments again. The results were presented at the 2010 American Society of Clinical Oncology (ASCO) annual meeting.
Herceptin is a targeted therapy used to treat advanced-stage, HER2-positive breast cancers and to lower the risk of recurrence (the cancer coming back) 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.
Paclitaxel is a taxane chemotherapy medicine often used to to reduce the risk of early-stage breast cancer coming back after surgery. Paclitaxel also is used to treat advanced-stage breast cancer, including metastatic breast cancer. Metastatic breast cancer is cancer that has spread outside the breast to another part of the body.
Metastatic breast cancer often stops responding to certain medicines after they have been used for a while. Doctors call this "treatment resistance." If treatment resistance happens, you'll usually be switched to one or more different medicines.
Afinitor is approved by the U.S. Food and Drug Administration to treat advanced-stage kidney cancer. Doctors are studying whether it can treat other cancers, including breast cancer.
Afinitor is an mTOR (mammalian target of rapamycin) inhibitor. mTOR is a type of protein called a kinase. Kinases help all cells (both normal and cancer cells) get the energy they need. When kinases don't act normally or are overactive they help certain breast cancers grow. Herceptin treats breast cancer by interfering with abnormal kinase activity linked to the HER2 protein. mTOR inhibitors work by interfering with the mTOR kinase.
The study reviewed here was a phase II study. Phase II studies help figure out the best dose of a new treatment that can be used safely without serious side effects. Phase II studies also help researchers figure out if a larger study involving more people makes sense.
In the study, 55 women diagnosed with metastatic, HER2-positive breast cancer that had stopped responding to Herceptin and/or taxane chemotherapy (such as Taxol) were treated with a combination of Herceptin, Taxol, and Afinitor.
Herceptin is given intravenously. Afinitor is a pill taken by mouth once every day. Paclitaxel is given intravenously 3 times in a 28 day cycle. The women got this treatment regimen until the cancer grew or unacceptable side effects developed.
The Afinitor-Herceptin-Taxol combination benefited 81% of the women:
The regimen controlled disease for 6 months or more in 40% of the women.
Both Herceptin and Afinitor may cause serious side effects, including heart and lung problems. Four of the women in the study (.07%) had serious lung problems. Developing mouth sores (called stomatitis) was the most common side effect, which happened in 20% of the women.
While this research seems promising, more research is needed so doctors understand the best way to use the Herceptin-Afinitor combination to treat breast cancer. Other experimental mTOR inhibitors also are being studied as treatments for breast and other cancers.
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 an mTOR inhibitor like Afinitor. 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.
Please help Breastcancer.org bring you the latest news on targeted therapies by making a tax-deductible donation today.
CHICAGO (MedPage Today) -- It appears that by adding the targeted agent everolimus (Afinitor) to the chemotherapy regimen of women whose advanced breast cancer is no longer sensitive to paclitaxel (Taxol) and trastuzumab (Herceptin), resistance can be switched off and response rates enhanced, researchers said here.
"We are reporting a median progression-free survival of 26 weeks," Fabrice Andre, MD, assistant professor of medicine at the Institute Gustav Roussy, Villejuif, France, told MedPage Today. "Most patients benefited from treatment."
"We also were able to see that the addition of everolimus has an acceptable safety profile in these patients," Andre said at his poster presentation here during the annual meeting of the American Society of Clinical Oncology.
In an open-label, multicenter Phase II study, researchers enrolled 55 women diagnosed with HER2 overexpressing metastatic breast cancer whose tumors were resistant to trastuzumab and taxane therapies.
The patients were treated with everolimus 10 mg/day; paclitaxel 80 mg/m2 on days I, 8 and 15 of a 28-day cycle; and trastuzumab 2/mg/kg a week after receiving a 4 mg/kg loading dose on Day 1. After completion of six cycles of the regimen, patients -- with concurrence of their physicians -- could continue on trastuzumab and everolimus. Treatment was continued until either the patient progressed or toxicity became unacceptable.
Nine patients -- 19% of the group -- achieved a partial response to treatment, Andre said, and another 30 patients (62%) achieved disease stabilization. That translates to a disease control rate of 81%. "The partial response and disease stabilization held for at least six months among 40% of the patients in the study," he said.
He said that the major adverse event that created the most distress among the patients was stomatitis, experienced by 20% of the patients -- although none of the patients experienced Grade 4 stomatitis. Four patients experienced Grade 3 pulmonary adverse events: pneumonia, interstitial pneumonitis and non-infectious pneumopathy.
The women in the trial were about 56 years of age, and 80% of them had visceral metastases. About 94% of the women had tumors that were resistant to trastuzumab, evidenced by progression while on treatment. About 89% were resistant to taxanes.
"The adverse events that we worry about are those involving the respiratory system," Edith Perez, MD, professor of medicine at the Mayo Clinic, Jacksonville, Fla., told MedPage Today. "These are interesting studies that show combining everolimus with chemotherapy and other target agents is feasible with promising results."
Andre said the results in the Phase II study appear to confirm results seen in Phase I work. He said a Phase III trial is recruiting patients.
Andre and colleagues disclosed financial relationships with Novartis, Pfizer and Genentech; Perez has disclosed financial relationships with Genentech, Novartis and Bayer.
Primary source: Journal of Clinical Oncology Source reference: Dalenc F et al, "Everolimus in combination with weekly paclitaxel and trastuzumab in patients (pts) with HER2-overexpressing metastatic breast cancer (MBC) with prior resistance to trastuzumab and taxanes: A multicenter phase II clinical trial" J Clin Oncol 2010; 28: Abstract 1013.
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