Biomedical Engineering Reference
In-Depth Information
with HER-2 amplification, the addition of lapatinib increased PFS (8.2
vs. 3 months) and objective response rate (28 vs. 15%). In contrast,
the addition of lapatinib did not result in a significant change in
either PFS or ORR in the patients without HER-2 amplification/
overexpression [99]. All together, these data are consistent with
HER-2 amplification/overexpression as a predictive biomarker
for response to lapatinib as a single agent, in combination with
chemotherapy, and in combination with aromatase inhibitors.
4.5.3
Pertuzumab
Pertuzumab is an antibody that inhibits the dimerization of HER-2
with other members of the EGFR family, thus inhibiting activity of
HER-2 [104-106]. Few studies have been reported in the literature
to date
2
. Two phase II trials measured the efficacy of pertuzumab
in combination with trastuzumab in patients that had HER-2
amplification in their tumors and whose tumors had progressed
on trastuzumab based therapies [107, 108]. The two studies found
objective responses in 16/66 (24%) and 2/11 (18%) and prolonged
stable disease in 17/66 (26%) and 3/11 (27%) for an overall clinical
benefit in approximately 50% of the patients. In contrast, a phase II
study investigated the efficacy of pertuzumab in patients with HER-2
negative tumors (FISH negative and/or IHC 0, 1+ or 2+) and found
very low rates of clinical benefit [109]. Partial responses were seen
in 2 of 78 (2.6% ) patients and stable disease lasting greater than 24
weeks in 4 of 78 (5%), resulting in a clinical benefit in approximately
7.7% of patients. The data are consistent with HER-2 amplification/
overexpression as a predictive biomarker although more data will
be needed to assess this fully.
Overall, the data support HER-2 amplification/overexpression
as a predictive biomarker for response to HER-2 targeted therapies
including trastuzumab, lapatinib, and pertuzumab in breast cancer.
4.6
HER-2 Amplification as a Predictive
Biomarker for Response to Chemotherapy
in Breast Cancer
HER-2 amplification or overexpression has been reported as a
predictive biomarker for the response to anthracyclines and taxanes.
