INST 0514C- Biologic Correlative Study: Trial of GW572016 in HER2 Overexpressing Breast Cancer Patients
Status:
Completed
Trial end date:
2009-10-01
Target enrollment:
Participant gender:
Summary
Neoadjuvant chemotherapy has become the standard of care for breast cancer patients with
large tumors in order to render them operable for mastectomy or, in some cases, for
lumpectomy and radiation therapy. Building on this theme, several large hormonal therapies
are extensively investigated in the neoadjuvant setting, together with biologic correlates
for response and resistance. As a further extension, neoadjuvant therapies with biologic
agents are now too, being investigated for biologic evidence of efficacy before large-scale
clinical trials of thousands of patients are embarked on. The neoadjuvant setting is
especially attractive for these studies for several reasons including early assessment of
response to therapy, biopsiable access to the primary tumor, and considerable reduced sample
sizes compared to those required in the adjuvant setting. In addition, clinical response to
neoadjuvant chemotherapy is a validated surrogate marker for improved survival. It may be
used to test the overall efficacy of neoadjuvant treatment regimens and mirrors the effect of
therapy on micrometastases setting. In a recent study, good clinical response to neoadjuvant
chemotherapy was the only independent variable, by multivariate analysis, associated with
decreased risk of death.
GW572016 is a new and promising dual tyrosine kinase inhibitor against HER1/2. Hundreds of
patients were treated in phase I and II studies world-wide and results indicate that this
reversible, oral small molecule is generally well-tolerated. Studies of neoadjuvant
Trastuzumab indicate that HER2 interference leads to significant tumor regression even after
3 weeks of monotherapy. We aim to extend these findings with a novel agent, GW572016 that may
be more effective, especially from its in vitro data, and to discover the true response rate
to inhibiting HER1/2 signal transduction in breast cancer patients.