Biomedical Engineering Reference
In-Depth Information
breast cancer that had progressed on trastuzumab treatment
and randomized them between lapatinib plus capecitabine and
capecitabine alone [95, 97]. The patients treated with lapatinib
plus capecitabine had an improved progression free survival and
response rate compared with those treated with capecitabine alone
[95, 97]. The second study enrolled patients with metastatic disease
to first line treatment with lapatinib plus paclitaxel or paclitaxel
alone [96]. This study included a preplanned retrospective analysis
of HER-2 amplification/overexpression by a central laboratory.
In patients whose tumors had amplified HER-2 (FISH+ defined by
HER-2/CEP17 ≥ 2.0 or IHC 3+ if FISH was not available) lapatinib
resulted in a statistically significant increase in the time to
progression (36 vs. 25 weeks), event-free survival (35 vs. 22 weeks),
and overall response rate (63 vs. 38%) compared with paclitaxel
alone [96]. By contrast, in the patients whose tumors did not have
amplified HER-2 lapatinib did not result in a statistically significant
increase in the time to progression (25 vs. 24 weeks), event-free
survival (23 vs. 23 weeks), and overall response rate (30 vs. 23%)
compared with paclitaxel alone [96]. Similar to the retrospective
analyses of the trastuzumab studies described above, Press
et al.
found that approximately 16% of the patients enrolled in the first
phase III study of lapatinib and capecitabine did not have amplified/
overexpressed HER-2 when the samples were centrally analyzed
[103]. HER-2 amplification was determined by FISH (HER-2/
CEP17 ≥ 2.0). Samples where FISH could not be performed were
considered positive with IHC 3+ staining. When the data from both
of the lapatinib phase III studies were analyzed, the overall response
rate and progression free survival were significantly improved when
lapatinib was added to chemotherapy in patients whose tumors
had amplification or overexpression of HER-2 [103]. There was no
benefit to lapatinib in the patients with tumors that did not have
amplification or overexpression [103]. Also, this analysis found no
relationship between the benefit of lapatinib and EGFR expression
[103].
A phase III study randomized patients with hormone receptor
positive metastatic breast cancer to first line treatment with either
lapatinib plus letrozole or placebo plus letrozole [99]. This study
included 219 patients with HER-2 amplification (FISH+ defined as
HER-2/CEP17 ≥ 2.0, IHC 3+, or IHC 2+ and gene amplification by
FISH) and 952 patients without HER-2 amplification. In the patients
