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Role of Lapatinib in HER2-Positive Breast Cancer

Panelists: Kimberly L. Blackwell, MD, Duke; Adam M. Brufsky, MD, PhD, University of Pittsburgh; Joyce A. O’Shaughnessy, MD, US Oncology; Mark D. Pegra
Published: Monday, Mar 17, 2014
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The TKI lapatinib has been studied across a variety of settings for patients with HER2-positive breast cancer. In the NSABP B41 study, patients received neoadjuvant cyclophosphamide and doxorubicin followed by weekly paclitaxel with trastuzumab, lapatinib, or lapatinib plus trastuzumab. The overall difference in pathologic complete response (pCR) rates were similar between trastuzumab (52.5%) and lapatinib (53.2%), moderator Adam M. Brufsky, MD, PhD notes. However, the combination showed a pCR of 62%, although this was not statistically significant.

In the adjuvant setting, the ALTTO trial explored adjuvant lapatinib alone, trastuzumab alone, trastuzumab followed by lapatinib, and lapatinib in combination with trastuzumab. However, the lapatinib alone arm was closed early, due to futility, Hope S. Rugo, MD, points out. Full results are expected later this year.

In the neoadjuvant setting, the NeoALTTO study found that the combination of lapatinib and trastuzumab improved pCR compared to either agent alone (51.3% versus 24.7%). These data suggest that lapatinib has an antiproliferative property, suggests Joyce A. O’Shaughnessy, MD. An update of the study found that pCR was significantly associated with longer survival at 3 years (94% versus 87%).

The collection of data so far indicates that lapatinib is inferior to trastuzumab and T-DM1 in the metastatic setting for patients with HER2-positive breast cancer, Kimberly L. Blackwell, MD, states. However, lapatinib may still have utility following progression on T-DM1 and pertuzumab-based regimens. In fact, Blackwell notes, the combination of lapatinib and trastuzumab recently gained approval in Europe for the treatment of patients following progression on trastuzumab.

Certain intricacies exist for the utilization of treatment with lapatinib, in terms of managing toxicity and tachyphylaxis, notes O’Shaughnessy. Lapatinib is approved for use with capecitabine for patients with HER2-positive breast cancer. In some situations, Rugo notes that she utilizes trastuzumab plus capecitabine or even lapatinib and trastuzumab. It does seem that both capecitabine and lapatinib can cross the blood-brain barrier for patients with brain metastases, Rugo suggests.

A small subset of patients with brain metastases was enrolled in the EMILIA trial, Blackwell notes. In an analysis of these patients, the severity of brain metastases was similar between the capecitabine plus lapatinib arm versus T-DM1 following treatment. As a result, Blackwell suggests that the presence of brain metastases should not be a determining factor between the use of lapatinib plus capecitabine or T-DM1.


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The TKI lapatinib has been studied across a variety of settings for patients with HER2-positive breast cancer. In the NSABP B41 study, patients received neoadjuvant cyclophosphamide and doxorubicin followed by weekly paclitaxel with trastuzumab, lapatinib, or lapatinib plus trastuzumab. The overall difference in pathologic complete response (pCR) rates were similar between trastuzumab (52.5%) and lapatinib (53.2%), moderator Adam M. Brufsky, MD, PhD notes. However, the combination showed a pCR of 62%, although this was not statistically significant.

In the adjuvant setting, the ALTTO trial explored adjuvant lapatinib alone, trastuzumab alone, trastuzumab followed by lapatinib, and lapatinib in combination with trastuzumab. However, the lapatinib alone arm was closed early, due to futility, Hope S. Rugo, MD, points out. Full results are expected later this year.

In the neoadjuvant setting, the NeoALTTO study found that the combination of lapatinib and trastuzumab improved pCR compared to either agent alone (51.3% versus 24.7%). These data suggest that lapatinib has an antiproliferative property, suggests Joyce A. O’Shaughnessy, MD. An update of the study found that pCR was significantly associated with longer survival at 3 years (94% versus 87%).

The collection of data so far indicates that lapatinib is inferior to trastuzumab and T-DM1 in the metastatic setting for patients with HER2-positive breast cancer, Kimberly L. Blackwell, MD, states. However, lapatinib may still have utility following progression on T-DM1 and pertuzumab-based regimens. In fact, Blackwell notes, the combination of lapatinib and trastuzumab recently gained approval in Europe for the treatment of patients following progression on trastuzumab.

Certain intricacies exist for the utilization of treatment with lapatinib, in terms of managing toxicity and tachyphylaxis, notes O’Shaughnessy. Lapatinib is approved for use with capecitabine for patients with HER2-positive breast cancer. In some situations, Rugo notes that she utilizes trastuzumab plus capecitabine or even lapatinib and trastuzumab. It does seem that both capecitabine and lapatinib can cross the blood-brain barrier for patients with brain metastases, Rugo suggests.

A small subset of patients with brain metastases was enrolled in the EMILIA trial, Blackwell notes. In an analysis of these patients, the severity of brain metastases was similar between the capecitabine plus lapatinib arm versus T-DM1 following treatment. As a result, Blackwell suggests that the presence of brain metastases should not be a determining factor between the use of lapatinib plus capecitabine or T-DM1.
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