EGFR inhibition has been of great interest as a potential treatment for researchers working in breast cancer. Unfortunatley, gelfitinib and Iressa phase II studies in heavily pre-treated patients did not show much activity.
This observation also appears to extend to another EGFR TKI, namely erlotinib. A phase II trial of erlotinib (as monotherapy of 150 mg/day) in locally advanced or metastatic breast cancer (n = 69) was conducted with 2 arms, both of which contained heavily pretreated patients. Cohort 1 (n = 47) examining disease progression on or after treatment with an anthracycline, a taxane, and capecitabine revealed 1 PR (23 weeks) and 6 SD (all >12 weeks). Cohort 2 (n = 22) examining disease progression on or after at least one chemotherapy regimen revealed 1 PR (16+ weeks) and 2 SD (both>8 weeks) (Winer et al. 2002). Again, the efficacy in these study groups was at best modest and the most common side effects were grade 1 and 2 skin rashes (78%) and diarrhoea (59%). Another phase II trial based on pre-clinical data of additional efficacy of combination of capecitabine with erlotinib had 24 patients in the trial. It found that erlotinib (100 mg/day), capecitabine and docetaxel were generally well tolerated and that there was no pharmacokinetic interaction between erlotinib, capecitabine and docetaxel or the metabolites of these drugs (Jones et al. 2003). At the same time, some patients anecdotally and in case reports, respond well to Tarceva. The explanation for this disrepancy my be that the sensitivity to Tarceva is determined by CK-2 activity in a particular patient. In any case, use of Tarceva at this time for breast cancer is experimental and warrants farther study.
A, Agrawal et al, Overview of tyrosine kinase inhibitors in.clinical breast cancer Endocr Relat Cancer July 1, 2005 12 S135-S144
RJ, Trigo J, Derosa F, Brennscheidt U, Rakhit A, Wright T, Carbonell Castellon X, Twelves C & Baselga J 2003 A Phase 1b study of Tarceva (erlotinib) plus capecitabine and docetaxel in metastatic breast cancer. Proceedings of the American Society of Clinical Oncology 22 45 (abstract 180).
Winer E, Cobleigh M, Dickler M, Miller K, Fehrenbacher L, Jones C & Justice R 2002 Phase II multicenter study to evaluate the efficacy and safety of Tarceva (erlotinib, OSI- 774) in women with previously treated locally advanced or metastatic breast cancer. Breast Cancer Research and Treatment 76 Abstract 445.
Yamasaki F, Zhang D, Bartholomeusz C, Sudo T, Hortobagyi GN, Kurisu K, Ueno NT.
Sensitivity of breast cancer cells to erlotinib depends on cyclin-dependent kinase 2 activity.Mol Cancer Ther. 2007 Aug;6(8):2168-77.
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