Targeted therapy and chemotherapy shrinks breast cancer metastases in brain

March 27, 2016

Lapatinib (Tykerb) and capecitabine (Xeloda) were paired in an extension of a Phase 2 clinical trial in which lapatinib given alone shrank brain metastases significantly in six percent of 241 patients.

In the extension trial, capecitabine was added to lapatinib in 49 patients whose metastases -- cancerous colonies in the brain spread from their primary cancer -- had progressed while on treatment. With the combination therapy, brain metastases shrank by 20 percent or more in 18 patients (37 percent) and shrank by at least 50 percent in 10 patients (20 percent), reported Nancy Lin, MD, of Dana-Farber's Breast Oncology Center.

"Very few medications have shown activity in the treatment of brain metastases, particularly in HER-2-positive metastatic breast cancer patients," said Lin, who led the study with Eric Winer, MD, director of the Dana-Farber Breast Oncology Center. "Therefore, these data are quite encouraging, and further studies are warranted."

The data (abstract 6076) will be presented on Sunday, Dec. 16 at 7 a.m. CT.

Lapatinib is an oral small-molecule drug from GlaxoSmithKline that is approved along with capecitabine for treating patients with advanced or metastatic breast cancer whose tumors are driven by the abnormal growth signal, HER-2, and who have already undergone therapy including trastuzumab (Herceptin), a taxane drug, and an anthracycline compound. Lapatinib, like trastuzumab, blocks the HER-2 signal.

Up to one-third of women with advanced, HER-2-positive breast cancer may develop metastases to the brain.

"Although radiation treatment is often effective, as women live longer with metastatic cancer, some develop worsening of brain metastases despite radiation," said Lin. "Because cancer in the brain can have a major impact on quality of life, it is important to have treatment options to address this problem."

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There were many more grade 2 and grade 3 tumors in women with the two rarer subtypes ?? 92 percent in HER2+ cancer and 91 percent in triple negative cancer ?? compared to HER2 negative/ER/PR+ cancer (36 percent). Tumors are graded 1-3, and higher grade tumors are more likely to grow faster and be more difficult to treat than lower grade tumors. Cancer came back more frequently in HER2+ tumors (7.4 percent of patients relapsed) and triple negative cancers (12.5 percent), compared to HER2 negative/ER/PR+ cancer (1.3 percent). Although the overall outcome of these small, lymph-node-negative tumors was excellent (overall survival 97.4 percent, disease free survival 95.1 percent), these outcomes were different in the three subgroups studied. The death rate was higher in triple negative breast cancer: there was one death in the 24 patients with triple negative tumors, none in the HER2+ group of 27 women, and one death related to relapse in 219 women with HER2 negative/ER/PR+ cancer.

Although only small numbers of women have the rarer cancer subtypes included in this study, the findings suggest that women with HER2+ and triple negative tumors should receive as much treatment as possible in order to prevent cancer relapse, Dr. Amar says. Researchers found that only 35 percent of women with triple negative cancer were treated with adjuvant chemotherapy (chemotherapy after surgery) despite the higher grade of the tumors. ???Chemotherapy may not work as well as we would like in these tumors, but, still, physicians who treat patients with triple negative cancer should be aware of the higher risk of relapse, even if tumors are quite small,??? she says.

Adjuvant chemotherapy was offered to 28 percent of patients with HER2+ tumors, and only 4 percent received the targeted therapy Herceptin, which has been designed specifically to treat this class of tumors. ???Should Herceptin be offered to such small node-negative tumors" There is not enough data currently to answer this question,??? Dr. Amar says. ???But this study definitely highlights the fact that HER2 positive tumors, even if very small, may warrant more aggressive therapy.???

Only 3.9 percent of patients with HER2 neg/ER/PR+ cancer were treated with chemotherapy. ???So although the rates of adjuvant chemotherapy use were significantly higher in the HER2+ and triple negative subgroups, these groups still showed a higher relapse rate,??? she says.

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