The study reviewed here found that the targeted therapy Tykerb (chemical name: lapatanib) may be effective against HER2-positive inflammatory breast cancer after other treatments don't work any more. Tykerb currently is approved to be given in combination with Xeloda (chemical name: capecitabine), a type of chemotherapy, to treat advanced, HER2-positive breast cancer that has stopped responding to anthracyclines, taxanes, and Herceptin (chemical name: trastuzumab).
This research was a phase II study, which means it is an small, early study looking at how effective a treatment is. Before a new treatment or new use for a treatment is approved, phase III studies must be done.
Inflammatory breast cancer is an uncommon but aggressive form of the disease. Symptoms of inflammatory breast cancer include swelling, redness, and tenderness of the breast. Surgery, chemotherapy, and radiation therapy are all used to treat inflammatory breast cancer. About 30% to 40% of inflammatory breast cancers are HER2-positive. The targeted therapy Herceptin also is used to treat HER2-positive inflammatory breast cancer.
In the study reviewed here, 126 women diagnosed with HER2-positive inflammatory breast cancer that had stopped responding to other treatments (including chemotherapy and Herceptin) were treated with Tykerb. Tykerb is a pill taken by mouth once a day.
This study suggests that Tykerb might be a good treatment for HER2-positive inflammatory breast cancer when the cancer stops responding to other treatments. Still, this research is early. More research is needed to figure out how beneficial and safe Tykerb is when used for this purpose.
If you've been diagnosed with inflammatory breast cancer, talk to your doctor about the results of this study and whether Tykerb might be an option for you. You and your doctor also may want to consider whether participating in a clinical trial on inflammatory breast cancer treatments might make sense for you.
Learn more in the Breastcancer.org Inflammatory Breast Cancer area.
SAN FRANCISCO, April 27 (MedPage Today) -- Lapatinib (Tykerb) may offer an option for inflammatory breast cancer when other treatments have failed, researchers said.
Lapatinib yielded tumor responses in 39% of women with HER2+ inflammatory breast cancer heavily pretreated with chemotherapy, including trastuzumab (Herceptin), Bella Kaufman, M.D., of the Chaim Sheba Medical Center in Tel Hashomer, Israel, and colleagues found.
In the phase II study, lapatinib responses lasted 20.9 weeks on average, a clinically meaningful effect, the researchers reported online in The Lancet Oncology.
Inflammatory breast cancer is an aggressive type with a higher frequency of HER2 overexpression than other breast cancers (40%).
Treatment is typically multimodal involving neoadjuvant combination chemotherapy followed by surgery, adjuvant chemotherapy, or radiotherapy.
For patients with tumors overexpressing HER2 who are refractory to or fail these treatments, there are currently no other options, Dr. Kaufman's group noted.
Since lapatinib is a tyrosine kinase inhibitor selective for HER2, the researchers tested its efficacy in a phase II study of 126 patients with relapsed or refractory HER2+ inflammatory breast cancer.
Prior treatment included more than four chemotherapy regimens for 61% of patients, trastuzumab for 75%, and more than three trastuzumab regimens for 9%.
All patients got lapatinib 1,500 mg once a day in a nonrandomized, open-label fashion.
None of the patients had a complete response, defined as disappearance of all measurable disease on combined clinically evaluable skin-disease criteria and RECIST criteria, although one had response as measured by skin disease only.
After a median 12.1 weeks of lapatinib, 39% of the women (95% confidence interval 30% to 48%) met the primary endpoint of an objective response with at least a 50% decrease in the extent of skin disease from baseline.
Looking only at the clinically evaluable skin-disease criteria, the objective response rate was 40% (95% CI 31% to 50%), but the rate by RECIST criteria that included only patients with measurable sites of locally advanced or metastatic disease at baseline was just 15% (95% CI 9% to 24%).
Response rates were lower in patients previously treated with trastuzumab (35% versus 48%). But among those who responded, median overall survival after the first lapatinib dose was not significantly different for those who had prior trastuzumab treatment (18.4 versus 14.0 months).
In fact, patients with prior trastuzumab exposure who responded to lapatinib had the longest survival of any group, followed by those who responded without prior trastuzumab treatment.
"This finding confirms the clinical benefit of targeted therapy in these patients," Dr. Kaufman's group said.
Adverse event rates and severity were similar to that seen in prior lapatinib monotherapy studies.
Although 32% of patients had at least one serious adverse event, most were judged to be not treatment related. The most common of these were dyspnea (6%) and pleural effusion (4%).
Five patients (4%) died from adverse events considered to be possibly treatment related: one case of acute hepatitis and abdominal sepsis; one case of dyspnea, cyanosis, and pyrexia; one of pulmonary edema; one of superior mesenteric artery syndrome; and one case of jaundice.
However, the researchers noted, these fatal serious adverse events were also possibly related to underlying disease. "The cause of these events is difficult to discern because of the poor clinical outcome inherent in this heavily pretreated population of patients with inflammatory breast cancer."
The study was funded by GlaxoSmithKline.
Five of the researchers reported being employees or former employees of GlaxoSmithKline and holding stock in the company. One reported serving as a consultant to GlaxoSmithKline for the development of a skin scale of measurement for another trial, receiving travel grants from the company, and having given expert testimony at FDA and Health Canada presentations. Another reported having received honoraria from GlaxoSmithKline.
Primary source: The Lancet Oncology Source reference: Kaufman B, et al "Lapatinib monotherapy in patients with HER2-overexpressing relapsed or refractory inflammatory breast cancer: final results and survival of the expanded HER2+ cohort in EGF103009, a phase II study" Lancet Oncol 2009; DOI:10.1016/S1470-2045(09)70087-7.
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