Lapatinib Plus Trastuzumab Improves Survival in Metastatic Breast Cancer

In patients with heavily pretreated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer, combination treatment with lapatinib and trastuzumab was associated with a median survival benefit of 4.5 months, according to the final results of a phase III study.¹

In 17% to 30% of breast cancer cases, the HER2 gene is amplified or its product overexposed, which is associated with a more negative prognosis. Trastuzumab and lapatinib are the 2 available medications that can inhibit HER2-mediated signaling, and their use in combination is a beneficial strategy because each drug offers specific clinical benefit. Researchers previously determined that using these drugs in combination significantly improved progression-free survival (PFS).² In this new study, the researchers report how combination treatment with lapatinib and trastuzumab, compared with lapatinib monotherapy, affect overall survival.

Among 291 patients (132 in the lapatinib group and 131 in the lapatinib plus trastuzumab group), those in the combination therapy group had significantly improved PFS and a longer median overall survival (14 months vs 9.5 months for the monotherapy group). At 6 months and 12 months, the improvement in absolute overall survival rate was 10% and 15%, respectively, in the combination group compared with the monotherapy group. Interestingly, patients who had 1 to 3 previous trastuzumab regimens had a greater benefit (7 to 8 months) than patients who had 4 or more previous regimens. In addition, median survival postprogression was 10.7 months for the combination group and 6.4 months for the lapatinib group.

Nearly all patients in each group experienced adverse events, with diarrhea, nausea, rash, fatigue, and vomiting being the most common. The median improvement in survival was 4.5 months, which is similar to other studies using trastuzumab as an adjunct to chemotherapy as first-line treatment of HER2-positive metastatic breast cancer.^3,4

Pertinent Points:
- Compared with lapatinib monotherapy, combination treatment with lapatinib and trastuzumab offers a 29% reduction in risk of death for patients with HER2-positive metastatic breast cancer.
- Median overall survival was improved by 4.5 months with combination therapy compared with monotherapy.
- The optimal setting for combining anti-HER2 agents is unknown, but this treatment strategy seems beneficial and may allow the patient to take a break from chemotherapy for a time, say the the study authors.
- Patients who received 1 to 3 regimens of trastuzumab prior to combination therapy had a greater improvement in overall survival, suggesting that dual HER2 blockade should be considered early in treatment for metastatic disease.

References:

1. Blackwell KL, Burstein HJ, Storniolo AM, 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. 2012;30:2585-2592.
2. Blackwell KL, Burstein JH, Storniolo AM, et al. Randomized study of lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010;28:1124-1130.
3. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer than overexpresses HER2. N Engl J Med. 2001;344:783-792.
4. Burstein HJ, Kuter I, Campos SM, et al. Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2001;19:2722-2730.