Dovepress ovepress.com of patients with refractory Rer disease, the use of paclitaxel and lapatinib combination is supported patients with taxane-resistant MBC and � stable disease 2 weeks in seven patients.27 A big e multicenter, randomized, GDC-0879 double-blind phase III study investigated the combination of lapatinib and paclitaxel for metastatic first line setting.17 A main objective of this study was to study the efficacy of lapatinib in patients with advanced tumors without HER2 amplification / overexpression. Women with HER2 negative or HER2-uncharacterized MBC were randomized to paclitaxel 175 mg/m2 iv every 21 days, more than 1500 mg of lapatinib once t Of possible or placebo. Or were reported in 35% and 25.3% of patients in the paclitaxel and paclitaxel-lapatinib arm placebo.
However, there was no significant difference NVP-TAE684 in TTP or OS between the treatment groups. From a pre-established, retrospective, blinded, with central analysis of tumor tissue for HER2 IHC and FISH, 86 patients were found to be HER2-positive disease. For patients with fish-and IHC, there was, as expected, a strong association between HER2 gene amplification and HER2 protein overexpression. For HER2-negative patients, no difference was observed for any outcome. But is entered for the minority of HER2-positive, treatment with lapatinib / paclitaxel Born statistically significant improvement in TTP, event-free survival, ORR and CBR. No significant benefit observed OS. These patients are not very numerous, and were not randomized according to HER2 status, but they were also balanced between treatment groups.
Median TTP paclitaxel / lapatinib treated HER2 postive patients was 36.4 weeks versus 25.1 weeks in patients with paclitaxel / placebo. In the paclitaxel / lapatinib compared with patients in the paclitaxel / placebo, ORR and CBR were markedly Ago. Thus, additionally Tzlicher advantage of lapatinib reported that women with HER2 verst the disease RKT, suggesting that lapatinib exerts its prime Ren effects through inhibition of the HER2 pathway. Despite Lapatinib is a kinase inhibitor with dual EGFR showed no correlation with clinical efficacy. This vorl Ufigen results generate hypotheses require prospective Best Confirmation. An ongoing prospective study is the first line of lapatinib and paclitaxel w Rate 80 mg/m2 weekly in HER2-positive MBC.
Lapatinib first line endocrine substances, despite the documentation of HER2-positive and hormone receptor-positive MBC in the show, many patients resistant to anti-retroviral therapy, HER2 and / or hormone therapy. A m Glicher mechanism of resistance is through talk between ErbB2 and downstream signaling pathways in HR. Can overcome Dual blockade of the HER2 and HR talk about this and improve outcomes. Endocrine Therapy in HER2-positive, HR-positive, in which HER2 overexpression can confer resistance to hormone therapy can inhibit the simultaneous HR and ErbB2-addict Be effective. In addition, HR-positive tumors, HER2-negative, early use of ErbB inhibitors can prevent or limit the up-regulation of ErbB pathways that h Frequently in the progression of disease.28 For this purpose, several targeted agents in combination with hormonal therapy anastrozole plus trastuzumab 0.29 31 showed an improvement in the survival period without endocrine blockade alone in women with HR positive HER 2-positive MBC studies, and