Joe
10-13-2004, 10:34 AM
Study finds no connection between trastuzumab and brain metastases
Median overall survival was similar in patients with metastases regardless of trastuzumab treatment.
By Tammy Dotts
Staff Writer
October 2004
Doctors may be able to set aside concerns that trastuzumab (Herceptin, Genentech) therapy for breast cancer could create a sanctuary in the brain where micrometastases could continue to develop.
A study at the Memorial Sloan-Kettering Cancer Center in New York found no increased risk of central nervous system (CNS) metastases in patients who received trastuzumab, compared with those who did not.
The researchers did not find a survival difference based on trastuzumab therapy for patients who received trastuzumab. ôThe long median survival after the diagnosis of brain metastases suggests that, even in patients with systemic stage-4 disease, vigorous treatment of CNS metastases can improve clinical outcomes,ö wrote senior author Lauren E. Abrey, MD, a neurologist at Sloan-Kettering.
Abrey and her colleagues suggested a large prospective cohort study to further examine the risk of CNS metastases associated with trastuzumab. ôMeanwhile, to prolong survival, we have to rely on prompt clinical diagnosis and aggressive treatment for patients with CNS metastases,ö she wrote.
Sanctuary theory
Trastuzumab does not cross the blood-brain barrier. In theory, this could create a sanctuary where micrometastases could proliferate after systemic metastases were eliminated. Oncologists have observed frequent CNS recurrences after trastuzumab, and a retrospective study found 34% of trastuzumab-treated patients had brain metastases. That study, however, did not compare metastasis occurrence between patients who did and did not receive trastuzumab.
Abrey and her colleagues initiated their retrospective study to evaluate the incidence of metastases by trastuzumab status. ôIf we had found a clinically significant increase in risk,ö she wrote, ôthen routine screening for CNS metastases or prophylactic CNS therapy may have been considered in future studies.ö
The researchers used Sloan-KetteringÃâ€*s breast oncology neuroimaging and trastuzumab databases to identify patients. They ended with a cohort of 79 patients who received trastuzumab and 264 patients who did not. A cranial magnetic resonance imaging or computed tomography scan was available for all patients.
There was no significant difference between the two patient groups for the incidence of all CNS metastases, of brain metastases alone or of leptomeningeal metastases alone, according to the study.
The lack of significance remained after researchers adjusted for other possible prognostic factors: HER-2/ neu status, estrogen-receptor and progesterone-receptor status, age at diagnosis, positive lymph node status and lung, liver, bone and other organ metastases.
HER-2/ neu status was missing for 32% of patients, and about 47% of patients in the trastuzumab group were HER-2/ neu positive. The researchers stratified patients according to HER-2/ neu status and again found no significant difference in the incidence of metastases. They added, however, that the small size of the stratified subgroups prevented a definitive conclusion.
The median overall survival of patients with CNS metastases was not significantly different between the two patient groups: 26.3 months in the nontrastuzumab group and 24.9 months in the trastuzumab group.
The study appeared in Cancer.
For more information:
Lai R, Dang CT, Malkin MG, Abrey LE. The risk of central nervous system metastases after trastuzumab therapy in patients with breast carcinoma. Cancer. 2004;101:810-816.
Median overall survival was similar in patients with metastases regardless of trastuzumab treatment.
By Tammy Dotts
Staff Writer
October 2004
Doctors may be able to set aside concerns that trastuzumab (Herceptin, Genentech) therapy for breast cancer could create a sanctuary in the brain where micrometastases could continue to develop.
A study at the Memorial Sloan-Kettering Cancer Center in New York found no increased risk of central nervous system (CNS) metastases in patients who received trastuzumab, compared with those who did not.
The researchers did not find a survival difference based on trastuzumab therapy for patients who received trastuzumab. ôThe long median survival after the diagnosis of brain metastases suggests that, even in patients with systemic stage-4 disease, vigorous treatment of CNS metastases can improve clinical outcomes,ö wrote senior author Lauren E. Abrey, MD, a neurologist at Sloan-Kettering.
Abrey and her colleagues suggested a large prospective cohort study to further examine the risk of CNS metastases associated with trastuzumab. ôMeanwhile, to prolong survival, we have to rely on prompt clinical diagnosis and aggressive treatment for patients with CNS metastases,ö she wrote.
Sanctuary theory
Trastuzumab does not cross the blood-brain barrier. In theory, this could create a sanctuary where micrometastases could proliferate after systemic metastases were eliminated. Oncologists have observed frequent CNS recurrences after trastuzumab, and a retrospective study found 34% of trastuzumab-treated patients had brain metastases. That study, however, did not compare metastasis occurrence between patients who did and did not receive trastuzumab.
Abrey and her colleagues initiated their retrospective study to evaluate the incidence of metastases by trastuzumab status. ôIf we had found a clinically significant increase in risk,ö she wrote, ôthen routine screening for CNS metastases or prophylactic CNS therapy may have been considered in future studies.ö
The researchers used Sloan-KetteringÃâ€*s breast oncology neuroimaging and trastuzumab databases to identify patients. They ended with a cohort of 79 patients who received trastuzumab and 264 patients who did not. A cranial magnetic resonance imaging or computed tomography scan was available for all patients.
There was no significant difference between the two patient groups for the incidence of all CNS metastases, of brain metastases alone or of leptomeningeal metastases alone, according to the study.
The lack of significance remained after researchers adjusted for other possible prognostic factors: HER-2/ neu status, estrogen-receptor and progesterone-receptor status, age at diagnosis, positive lymph node status and lung, liver, bone and other organ metastases.
HER-2/ neu status was missing for 32% of patients, and about 47% of patients in the trastuzumab group were HER-2/ neu positive. The researchers stratified patients according to HER-2/ neu status and again found no significant difference in the incidence of metastases. They added, however, that the small size of the stratified subgroups prevented a definitive conclusion.
The median overall survival of patients with CNS metastases was not significantly different between the two patient groups: 26.3 months in the nontrastuzumab group and 24.9 months in the trastuzumab group.
The study appeared in Cancer.
For more information:
Lai R, Dang CT, Malkin MG, Abrey LE. The risk of central nervous system metastases after trastuzumab therapy in patients with breast carcinoma. Cancer. 2004;101:810-816.