Lapatinib side effects documented at this yr. ASCO:

[RobinP]

Well, as far as adjuvant laptanib, it appears there are side effects to be concerned with. The one that surprised me was alopecia, which is not seen with Herceptin. Maybe this in itself will make Herceptin more preferred for future adjuvant treatments, if Lapatinib is comparable to H. for efficacy.
<table border="0" cellpadding="0" cellspacing="3" width="98%"><tbody><tr><td nowrap="nowrap" valign="top" width="1%">Abstract No:

</td> <td valign="top" width="99%"> 1011

</td> </tr> <tr> <td nowrap="nowrap" valign="top" width="1%">Citation:

</td> <td valign="top" width="99%"> Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 1011

</td> </tr> <tr> <td nowrap="nowrap" valign="top" width="1%">Author(s):

</td> <td valign="top" width="99%"> A. Di Leo, H. Gomez, Z. Aziz, Z. Zvirbule, M. Arbushites, C. R. Oliva, M. Koehler, L. S. Williams, J. Dering, R. S. Finn

</td> </tr> <tr> <td nowrap="nowrap" valign="top" width="1%">Abstract:

</td> <td valign="top" width="99%"> Background: L is an oral tyrosine kinase inhibitor of EGFR/HER2, active as monotherapy and in combination for HER2-overexpressing advanced/metastatic breast cancer (BC). A Phase I study of L with paclitaxel (P) indicated no unexpected adverse events (AEs). PK profile indicated no relationship between peak plasma concentration of P+L and neuropathy, neutropenia, diarrhea, rash or myalgia. We report here blinded efficacy and safety data for patients (pts) with incurable Stage IIIb/IIIc/IV BC at first diagnosis or relapse, untested or negative (0/1+ IHC or FISH neg) for HER2. Unblinded data will be presented at ASCO 2007. Methods: Between Jan 2004 and Jul 2005, 580 pts from 24 countries were stratified by metastatic site and randomized 1:1 to L 1500 mg QD + 175 mg/m² P q3w or placebo QD + 175 mg/m² P q3w. Primary endpoint was TTP; secondary endpoints were AEs, ORR, PFS, CBR, RFS, and OS. Tumor tissue was obtained from the most recent biopsy of 451 (78%) pts and was centrally analyzed in blinded fashion for biomarker patterns. Serum samples were collected for central EGFR and HER2 ECD analysis. Results and Conclusions: 579 pts were analyzed; 87% presented with Stage IV BC. 55% received prior adjuvant chemotherapy or anti-hormonal therapy. No pts received previous trastuzumab. At the time of analysis, 561 (97%) pts progressed or otherwise withdrew. Most common AEs were alopecia (58%), neurological (55%, gr=3:8%), diarrhea (42%, gr=3:9%), nausea (32%), and rash (32%, gr=3:2%). Neutropenia and thrombocytopenia AEs related to study treatment were 18% and <1%, respectively. LVEF decrease of 20% relative to baseline and below LLN was reported 15 times. 12% of AEs led to treatment withdrawal. Blinded data analysis revealed a median TTP of 25 wks and ORR of 30%. CNS relapse was reported in 11 pts (2%). Enrollment predominantly came from countries with limited HER2 testing capacity thus a subgroup of pts is expected to be HER2+ve. Blinded analyses of HER2, ER and PR are ongoing at this time and final biomarker evaluations will be presented with unblinded efficacy data.

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