A final data analysis of the study EGF104900, which compared lapatinib (Tykerb) plus trastuzumab (Herceptin) to lapatinib alone, found the combination therapy resulted in a significant increase in overall survival in women with HER2 positive metastatic breast cancer. Overall survival is the time study participants lived after beginning trial treatment.
Lapatinib is a pill that targets human epidermal growth factor receptor 2 (HER2) and human epidermal growth factor receptor 1 (EGFR or HER1), two proteins that can be overexpressed in breast cancer. The HER proteins aid abnormal cell growth.
Trastuzumab is a targeted antibody therapy given by vein that attaches to and blocks HER2 receptors, slowing the growth of cancer cells.
Together, the two medicines offer a chemotherapy-free treatment option for women with HER2 positive metastatic breast cancer.
This phase III study compared the clinical benefits of combination therapy to lapatinib alone in 296 women with HER2 positive metastatic breast cancer whose disease had progressed on trastuzumab. All participants had been treated previously with anthracycline and taxane therapies, with the most recent cancer progression during trastuzumab therapy for HER2 positive metastatic disease. The women were randomly assigned treatment with either the combination therapy or lapatinib alone.
At a data cut off in June 2007, the lapatinib plus trastuzumab combination showed a significant improvement in progression-free survival, or time after treatment begins that cancer does not grow. Overall survival data was cut off in January 2009.
Current Analysis Findings
The final results, analyzed from overall survival data collected after the 2009 cutoff date, were published in the Journal of Clinical Oncology in July 2012. The researchers examined the data to present updated progression-free and overall survival findings and to identify participant subgroups with the best response to the combination therapy.
The findings include:
- A statistically significant (unlikely to have happened by chance) 4.5-month improvement in overall survival with combination treatment compared to lapatinib alone (median 14 months versus median 9.5 months, respectively).
- A 10 percent improvement over the lapatinib group in overall survival at six months of combination treatment, which grew to 15 percent improvement in overall survival at 12 months.
- Median progression-free survival of 11.1 weeks for the combination arm, compared to 8.1 weeks for lapatinib alone.
- The inclusion of crossover participants, participants who changed from the lapatinib-only arm to the combination arm, did not impact the statistical significance of overall survival data.
While researchers determined that combination therapy of lapatinib plus trastuzumab produced better results than lapatinib alone, factors such as site of metastasis, time from initial diagnosis to trial enrollment and number of metastatic sites may play a role in the treatment’s effectiveness.
Hormone sensitivity also impacted the treatment: women whose cancers were both HER2 positive and ER positive saw no difference in overall survival compared to their peers in the lapatinib-only arm, while women with HER2 positive, ER negative breast cancer had a significant improvement in overall survival over their peers.
In addition, overall survival improved more in women who had been treated with trastuzumab in the past for three or fewer cycles, versus women who had been treated with trastuzumab for four or more cycles.
Side effects were similar in both groups, with the most common being diarrhea, nausea, rash, fatigue and vomiting. Serious side effects affected 38 of the 149 participants in the combination arm, and 24 of the 146 participants receiving lapatinib alone.
What This Means for You
If you are being treated for HER2 positive metastatic breast cancer, talk to your doctor about the possibility of combination treatment with lapatinib and trastuzumab. Note that switching to combination therapy earlier may be more beneficial if your prior exposure to trastuzumab treatment was of a shorter duration.
Blackwell, Kimberly L., Burstein, Harold J., et al: Overall Survival Benefit With Lapatinib in Combination With Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: Final Results From the EGF104900 Study. J Clin Oncol. 30:21 (2585-92).