Dual HER2 Blockade With Lapatinib and Trastuzumab Improves Inhibition of Tumor Growth in HER2-Amplified Uterine Serous Carcinoma
In a retrospective analysis utilizing both uterine serous carcinoma cell lines and patient-derived xenografts, dual therapy with lapatinib (Tykerb) and trastuzumab (Herceptin) demonstrated antitumor responses, according to a study by Groeneweg et al in Clinical Cancer Research. Also, the authors hypothesized that the addition of lapatinib to trastuzumab therapy may have had a mitigating effect on trastuzumab resistance.
The effectiveness of biologic therapies that target HER2 has been well documented in patients with breast cancer. Researchers are now directing their focus on other cancer types that exhibit HER2 gene amplification, such as uterine serous carcinoma, which is an aggressive subtype of endometrial cancer.
Uterine serous carcinoma has been shown to harbor a 10% to 30% rate of HER2 gene amplification, with up to 70% of tumors exhibiting HER2 protein overexpression. Women with uterine serous carcinoma are at an increased risk for tumor recurrence as well as chemotherapy resistance. Thus, targeted biologic therapies may be of great benefit in this patient population.
Study Details
With that in mind, Groeneweg and colleagues investigated the effectiveness of HER2 inhibition using lapatinib and trastuzumab in patients with uterine serous carcinoma. Their study analyzed the medical records of 42 patients with uterine serous carcinoma who were treated surgically. Cell analysis was conducted both in vivo and in vitro. To affirm the presence of HER2, fluorescence in situ hybridization was performed on 5-μm–thick tissue sections. Samples with a HER2-to–chromosome 17 centromere ratio greater than 2.0 were considered amplified.
The researchers utilized nonimmortalized uterine serous carcinoma cell lines and uterine serous carcinoma patient–derived xenografts to evaluate the efficacy of lapatinib and trastuzumab as single agents and in combination therapy. Immunohistochemistry for HER2 revealed 2+ or 3+ protein expression in 55% of the cohort.
The median age of patients was 68.7 years. The average overall rate of survival was 2.4 years.
Lapatinib Active in HER2-Amplified Tumors
The in vivo part of this study indicated that lapatinib as a single agent and in combination with trastuzumab induced significant tumorstatic effects in tumors harboring HER2 gene amplification. In contrast, trastuzumab failed to induce any alterations in vitro or in vivo. The investigators noted that this was also evidenced in many other nonbreast adenocarcinomas found to harbor HER2-positive tumors.
Closing Thoughts
The results of this study suggest that HER2 gene amplification is a biomarker for response to HER2 inhibition in patients with uterine serous carcinoma. As for the potential for trastuzumab resistance, the authors hypothesized that the addition of lapatinib to trastuzumab therapy may have had a mitigating effect on trastuzumab resistance.
The investigators concluded, “These data support a potential role for dual anti-HER2 therapy in women with HER2 gene–amplified uterine serous carcinoma.”
Whitfield B. Growdon, MD, of the Vincent Center for Reproductive Biology, Vincent Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, is the corresponding author of the article in Clinical Cancer Research.
This research was funded by an institutional K12 Proton Share NCI Grant C06 CA059267 (WBG) and funding from the Advanced Medical Research Foundation (BRR) and Vincent Department of Obstetrics and Gynecology Research Funds (BRR). The study authors reported no conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
