The Repository @ St. Cloud State

Open Access Knowledge and Scholarship

Date of Award


Culminating Project Type


Degree Name

Applied Statistics: M.S.


Department of Mathematics and Statistics


College of Science and Engineering

First Advisor

Shiju Zhang

Second Advisor

Joyce Simones

Third Advisor

David Robinson

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Keywords and Subject Headings

HER2, meta-analysis, breast cancer, lapatinib, capecitabine, odds ratio



Breast cancer is the most common type of cancer in women despite advances in research and detection methods. Approximately 25 to 30 percent of newly diagnosed cases of breast cancer will overexpress HER2, human epidermal growth factor receptor 2, and are at a greater risk for disease progression and poorer clinical outcomes. The traditional treatment is associated with irreversible cardiac dysfunction. An alternative treatment involving lapatinib plus capecitabine has been reported in some randomized controlled clinical trials comparing treatment outcomes. To quantify the effectiveness of lapatinib plus capecitabine combination therapy versus capecitabine monotherapy in treating metastatic breast cancer, a systemic review seems necessary. In this thesis, meta-analysis was performed to synthesize the ratio of the odds of patient death or disease progression for breast cancer patients who are treated with a combination therapy to the odds for patients who are treated with monotherapy.


Several randomized clinical trials are identified comparing combination therapy lapatinib plus capecitabine versus capecitabine monotherapy in women with metastatic HER2 positive breast cancer that had disease progression after treatment with regimens that included an anthracycline, a taxane, and trastuzumab. Patients in the treatment arm received lapatinib dosed at 1,500 mg per day continuously plus capecitabine 2,000 mg per square meter of body surface area on days 1 through 14 of a 21 day cycle. Patients in the control arm received capecitabine at a dose of 2,500 mg per square meter of body surface area on days 1 through 14 of a 21 day cycle. Mantel–Haenszel fixed effect meta-analysis was used to combine the data to evaluate frequency of the events between combination therapy and monotherapy treatments in a heavily pre-treated metastatic breast cancer population.


Three eligible clinical trials were identified, reporting outcomes on 1,131 women. Mantel–Haenszel fixed effect analysis showed the event occurred 26.7 percent less frequently for women treated with combination lapatinib plus capecitabine (odds ratio [OR], 0.733; 95 percent confidence interval [CI], 0.565 to 0.952) than patients treated with capecitabine monotherapy. The use of lapatinib plus capecitabine should be evaluated in clinical trial for newly diagnosed HER2 positive patients or older patients who might otherwise be exposed to potential serious adverse side effects as a result of the current first line treatment or patients that have a pre-existing heart condition.


I dedicate my thesis work to my family who has taught me to apply an immense amount of work for the things that I aspire to achieve while continually offering love and support. I will appreciate all they have done; you are my best cheerleaders. A special gratitude to my sibling, Pamela, Janice, Sharon, Scott, Andrea, and Jenny, whose support and words of encouragement kept me motivated and driven to succeed.

To my mother, Marion, though absent, you are ever near, still missed, still loved, and ever dear. Your memory is my gift with which I’ll never part. I have you forever in my heart.



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