CHICAGO -- A combination therapy that included treatment with lapatinib (Tykerb) dramatically improved outcomes among metastatic breast cancer patients who experience metastases to the brain, researchers reported here.
The median overall survival for patients treated with trastuzumab (Herceptin) plus standard chemotherapy plus lapatinib had not been reached at 24 months of the study -- while the median overall survival for patients treated with trastuzumab and chemotherapy was 13 months, said Anna Berghoff, a fourth-year medical student and researcher at the Medical University of Vienna.
In a poster presentation at the 2011 annual meeting of the American Society of Clinical Oncology, Berghoff and her co-authors noted that when compared with treatments that were based on trastuzumab, the relative risk of death was reduced 72.1% when lapatinib was added to the treatment protocol (P=0.012).
"We suggest that until prospective data become available, patients with good performance status should receive lapatinib in addition to trastuzumab after completion of local therapy," Berghoff told MedPage Today. "Our study shows that additional treatment with lapatinib was associated with significantly better overall survival when compared with trastuzumab-based therapy alone."
She suggested that lapatinib has activity both against systemic breast cancer as well as specifically against breast cancer brain metastases.
In their retrospective study, the Austrian researchers reviewed data from all HER-2-positive breast cancer patients who developed brain metastases. They identified 225 women with breast cancer who were treated for brain metastases.
Of that group, 127 women were HER2-negative or had unknown HER2 status. These women were excluded from the analysis. The other 98 women were HER2-positive, but 18 of them were excluded because of poor performance status.
Most of the 80 women, average age 53, had a Karnofsky Performance Status greater than 70 (in the study population the median Karnofsky score was 80).
The women with brain metastases were identified from a breast cancer database, explained lead author Rupert Bartsch, MD, professor of medicine at the university. Twenty-eight women received trastuzumab plus or minus chemotherapy after completion of local therapy, he told MedPage Today in an email. Another 15 women were additionally treated with lapatinib.
There were 37 women who were treated prior to 2003 and therefore did not receive additional trastuzumab after completion of local treatment. "These women served as the control group," he said. Within this group, nine patients received chemotherapy while 28 had no further systemic treatment.
The researchers said that the median overall survival among the 28 women who were treated only with whole brain radiation after the appearance of brain metastases was about three months.
For the women who were treated with chemotherapy alone, but not with trastuzumab, median survival after brain metastases was about nine months.
Local therapy for these patients, according to the study protocol, consisted of whole brain radiotherapy. In patients with one to three brain metastases, surgical resection, radiosurgery, or boost irradiation was added.
"The proportion of HER2-positive patients with metastatic breast cancer who are dying of brain metastases instead of systemic disease progression has increased since the introduction of trastuzumab," Berghoff noted.
Bartsch explained that while trastuzumab is able to better control systemic disease, its impact on brain metastases has been limited. Breast cancer is the second most common cause of brain metastases, he said.
"The results seen in this trial may have something to do with lapatinib itself," suggested Jennifer Litton, MD, assistant professor of medical oncology at MD Anderson Cancer Center, Houston.
"Because it is a small molecule, lapatinib may have a direct effect on the brain metastases," she told MedPage Today, in commenting on the poster presentation.
The median overall survival for patients treated with trastuzumab (Herceptin) plus standard chemotherapy plus lapatinib had not been reached at 24 months of the study -- while the median overall survival for patients treated with trastuzumab and chemotherapy was 13 months, said Anna Berghoff, a fourth-year medical student and researcher at the Medical University of Vienna.
In a poster presentation at the 2011 annual meeting of the American Society of Clinical Oncology, Berghoff and her co-authors noted that when compared with treatments that were based on trastuzumab, the relative risk of death was reduced 72.1% when lapatinib was added to the treatment protocol (P=0.012).
"We suggest that until prospective data become available, patients with good performance status should receive lapatinib in addition to trastuzumab after completion of local therapy," Berghoff told MedPage Today. "Our study shows that additional treatment with lapatinib was associated with significantly better overall survival when compared with trastuzumab-based therapy alone."
She suggested that lapatinib has activity both against systemic breast cancer as well as specifically against breast cancer brain metastases.
In their retrospective study, the Austrian researchers reviewed data from all HER-2-positive breast cancer patients who developed brain metastases. They identified 225 women with breast cancer who were treated for brain metastases.
Of that group, 127 women were HER2-negative or had unknown HER2 status. These women were excluded from the analysis. The other 98 women were HER2-positive, but 18 of them were excluded because of poor performance status.
Most of the 80 women, average age 53, had a Karnofsky Performance Status greater than 70 (in the study population the median Karnofsky score was 80).
The women with brain metastases were identified from a breast cancer database, explained lead author Rupert Bartsch, MD, professor of medicine at the university. Twenty-eight women received trastuzumab plus or minus chemotherapy after completion of local therapy, he told MedPage Today in an email. Another 15 women were additionally treated with lapatinib.
There were 37 women who were treated prior to 2003 and therefore did not receive additional trastuzumab after completion of local treatment. "These women served as the control group," he said. Within this group, nine patients received chemotherapy while 28 had no further systemic treatment.
The researchers said that the median overall survival among the 28 women who were treated only with whole brain radiation after the appearance of brain metastases was about three months.
For the women who were treated with chemotherapy alone, but not with trastuzumab, median survival after brain metastases was about nine months.
Local therapy for these patients, according to the study protocol, consisted of whole brain radiotherapy. In patients with one to three brain metastases, surgical resection, radiosurgery, or boost irradiation was added.
"The proportion of HER2-positive patients with metastatic breast cancer who are dying of brain metastases instead of systemic disease progression has increased since the introduction of trastuzumab," Berghoff noted.
Bartsch explained that while trastuzumab is able to better control systemic disease, its impact on brain metastases has been limited. Breast cancer is the second most common cause of brain metastases, he said.
"The results seen in this trial may have something to do with lapatinib itself," suggested Jennifer Litton, MD, assistant professor of medical oncology at MD Anderson Cancer Center, Houston.
"Because it is a small molecule, lapatinib may have a direct effect on the brain metastases," she told MedPage Today, in commenting on the poster presentation.
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