Dr. Spector at ASCO and Lapatinib Sucess...

[RobinP]

Great news so far for Lapatinib in Dr. Spector's et. al. abstract . Not only was Lapatinib effective in her1 and her2 bc but it also was effective in patients with her3 and increased IGF. Not to mention it also worked when pTen was absent. Of course, you had to definately have her2 positivity, leaving triple negatives out of the game with this drug. See abstract for yourself below: PS.I just love how GSK is investigating the biological markers for Lapatinib, defining the target population better. Hats off for Dr. Spector and GSK reseachers!


EGF103009, a phase II trial of lapatinib monotherapy in patients with relapsed/refractory inflammatory breast cancer (IBC): Clinical activity and biologic predictors of response.

Sub-category:


Category:


Meeting:

2006 ASCO Annual Meeting


Abstract No:

502

Citation:

Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 502

Author(s):

N. L. Spector, K. Blackwell, J. Hurley, J. L. Harris, D. Lombardi, S. Bacus, S. B. Ahmed, H. Boussen, M. Frikha, F. B. Ayed

Abstract:

Background: Data from preclinical studies and small numbers of IBC patients inPhase I clinical trials suggest that IBC may be particularly sensitive to the anti-tumor effects of lapatinib, an inhibitor of ErbB1/ErbB2 tyrosine kinases. EGF103009 was initiated to confirm and expand these initial observations and identify a tumor profile predicting for the sensitivity of IBC to lapatinib. Methods: Patients with relapsed/refractory IBC based on clinical criteria, were assigned to Cohort A (ErbB2 overexpressors: 2/3+ IHC/FISH+) or B (ErbB1 +/ErbB2 non-overexpressors) after analysis of a fresh tumor biopsy in a central reference lab. Patients received lapatinib daily (1500mg/d). Clinical response was documented at day 56 and in the case of CR/PR, confirmed on day 84 and every 8 weeks thereafter. Target lesions were assessed according to RECIST criteria and response in skin disease documented by digital photography. Tumor expression of ErbB2, p-ErbB2, ErbB1, p-ErbB3, IGF-IR, PTEN, ER/PR, E-cadherin, β-catenin, and Rho B/C was analyzed by quantitative IHC from a fresh, pre-treatment biopsy. Results: Of 34 patients enrolled, clinical response data is available from 22 patients of which 17 had biopsies analyzed at a reference lab and assigned to Cohorts A (N=11) and B (N=6). Eight of 11 patients (72%) in Cohort A had a clinical response (CR/PR) to lapatinib documented by RECIST, skin disease, or both. There were no responders in Cohort B. All responders (i) overexpressed ErbB2 (2/3+ IHC or FISH+), (ii) increased p-ErbB2 (2/3+), (iii) co-expressed IGF-IR, and (iv) expressed activated, p-ErbB3. PTEN status did not affect response to lapatinib. Toxicity was generally grade I/II skin and G.I. with one grade III cardiotoxicity necessitating withdrawal from study. Conclusions: ErbB2 overexpression but not ErbB1 expression alone, predicts for sensitivity to lapatinib in IBC. High ErbB2, p-ErbB2 and IGF-IR co-expression predict for clinical response to lapatinib monotherapy in patients with relapsed/refractory IBC, illustrating the importance of selecting patients based on biology rather than histology alone, to maximize the clinical efficacy of ErbB kinase inhibitors in breast carcinomas.

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