Randomized Study of Lapatinib Alone or in Combination With Trastuzumab in Women With ErbB2-Positive, Trastuzumab-Refractory Metastatic Breast Cancer

Abstract

Despite disease progression on prior trastuzumab-based therapy, lapatinib in combination with trastuzumab significantly improved PFS and CBR versus lapatinib alone, thus offering a chemotherapy-free option with an acceptable safety profile to patients with ErbB2-positive MBC.

Increased overall survival independent of RECIST response in metastatic breast cancer patients continuing trastuzumab treatment: evidence from a retrospective study

“…Two recent randomized clinical trials have documented the benefit on overall response of continued use of trastuzumab in women with HER2 positive breast cancer who experienced progression during trastuzumab treatment [7,8]. Here we show from a study of clinical practice in Italy that continued trastuzumab treatment after disease progression has clinically and statistically significant effects, remarkably in both RECIST responder and non-responder MBC patients upon first line trastuzumab treatment.…”

“…Several retrospective studies published thus far (reviewed in [3,4]) [5,6] have indicated a certain overall response rate, clinical benefit and extended time to progression from the use of a second trastuzumabcontaining regimen in HER2-positive MBC patients who progressed on first-line trastuzumab treatment. Moreover, two recent randomized trials designed to directly evaluate the efficacy of continuing trastuzumab after progression demonstrated the potential clinical utility of continuing trastuzumab even for patients with progressive disease [7,8]. To further evaluate the benefits of trastuzumab-continuation therapy we carried out a retrospective analysis of 272 HER2 positive MBC patients first line trastuzumab treated in the metastatic setting at different oncology centers in Italy, who continued or discontinued trastuzumab at progression.…”

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

“…Similarly, data suggest that lapatinib has a more‐favorable cardiac risk profile than trastuzumab7, 47 and the combination of both does not appear to be more cardiotoxic than the use of trastuzumab alone 6. Trials of ado‐trastuzumab suggest low rates of cardiotoxicity during follow‐up to date 9…”

“…Development of the monoclonal antibody that targets the extracellular domain of HER2, trastuzumab, revolutionized the care of these patients, leading to large improvements in disease‐free and overall survival 5. In addition, development of newer anti‐HER2 therapies has led to further improvements in cancer outcomes for this population 6, 7, 8, 9…”

Towards Sustained Silencing of HER2/neu in Cancer By Epigenetic Editing

“…Approaches to improve blocking of the Her2/neu function through combination of Her2/neu-targeting therapies indeed showed improved response rates compared with monotherapy in vitro, in vivo (14,15), and in clinical studies (16). Another application is through exploiting Her2/neu as a targeting device for antitumor agents.…”