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Addition of Trastuzumab to Chemotherapy Produces 50% Increase in Survival in Patients Selected by FISH

Addition of Trastuzumab to Chemotherapy Produces 50% Increase in Survival in Patients Selected by FISH

Results from three retrospective
studies demonstrated that fluorescence in situ hybridization (FISH) testing of
tumor tissue for HER2 gene amplification is an effective method of selecting
women with HER2-positive metastatic breast cancer who will most likely respond
to trastuzumab (Herceptin) therapy. Data from these studies were presented at
the 37th annual meeting of the American Society of Clinical Oncology (ASCO).

In the retrospective analysis of tumor tissue from women in
the phase III pivotal combination trial, those who were positive for HER2 gene
amplification by FISH testing survived 50% longer—27 vs 18 months—when
treated with trastuzumab plus chemotherapy, as compared to those who received
chemotherapy alone.

This result contrasts with the 24% increase in survival seen
when the same tumors tested positive for HER2 protein overexpression by
immunohistochemistry testing.

Pivotal Trial

In the phase III pivotal first-line combination trial of
trastuzumab, lead author Dr. Robert Mass (a clinical scientist at Genentech) and
colleagues retrospectively tested and analyzed tumor tissue from 458 of 469
patients. The goal of the trial was to determine how HER2 gene amplification,
measured by FISH, compared with HER2 protein overexpression measured by
immunohistochemistry in identifying patients for trastuzumab therapy. HER2
levels of 2+ and 3+ measured by immunohistochemistry were required for
enrollment. (Overexpression is determined on a scale of 0 to 3+.)

Using the PathVysion FISH assay system, HER2 gene
amplification was detected in 76% of the study population. Among those who
tested positive by FISH, 89% were 3+ by immunohistochemistry and 31% were 2+. In
the subgroup of FISH-positive patients, the addition of trastuzumab to
chemotherapy resulted in an increase in the response rate to 54%, compared to
31% for those receiving chemotherapy alone. No improvement in response rates was
seen in women whose tumors were negative for HER2 gene amplification by FISH
(38% for trastuzumab with chemotherapy vs 37.5% for chemotherapy alone).

"These extensive retrospective analyses show us that
measuring gene amplification with FISH testing may provide more accurate
information about potential tumor response rates and improvement in survival
with Herceptin," said Dr. Mass.

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