"Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer".
The New England Journal of Medicine. 2012. PubMed•Full text•PDF

Clinical Question

Does Trastuzumab Emtansine (T-DM1) prolong progression-free and overall survival compared to lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane?

Bottom Line

Trastuzumab Emtansine (T-DM1) significantly improved progression-free and overall survival with less toxicity than lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane.

Major Points

Guidelines

This trial influenced clinical practice and treatment guidelines by providing evidence for the use of T-DM1 as a treatment option in HER2-positive advanced breast cancer.

Design

- Multicenter, randomized, open-label, phase 3 trial.
- N=991 patients with HER2-positive unresectable locally advanced or metastatic breast cancer.
- T-DM1 (n=495) vs. Lapatinib plus Capecitabine (n=496).
- Stratification factors included world region, prior chemotherapy regimens for advanced disease, and disease involvement (visceral vs. nonvisceral).
- Median follow-up: approximately 13 months (progression-free survival), 19 months (overall survival).

Population

- Inclusion criteria: Progression on or after most recent treatment for advanced disease or within 6 months after adjuvant therapy, HER2-positive status confirmed by central laboratory.
- Exclusion criteria: Prior treatment with T-DM1, lapatinib, or capecitabine; significant cardiovascular disease; CNS metastases.
- Median age: 53 years
- Median duration of follow-up: 19.1 months for the primary analysis of overall survival.

Interventions

- T-DM1 at 3.6 mg/kg IV every 21 days.
- Lapatinib at 1250 mg orally once daily plus Capecitabine at 1000 mg/m^2 orally every 12 hours on days 1-14 of a 21-day cycle.

Outcomes

- Primary Outcomes:
- Independent review assessed progression-free survival: 9.6 months (T-DM1) vs 6.4 months (control) (HR 0.65; 95% CI, 0.55-0.77; P<0.001).
- Overall survival at second interim analysis: 30.9 months (T-DM1) vs 25.1 months (control) (HR 0.68; 95% CI, 0.55-0.85; P<0.001).
- Secondary Outcomes:
- Investigator-assessed progression-free survival: 9.4 months (T-DM1) vs 5.8 months (control) (HR 0.66; P<0.001).
- Objective response rate: 43.6% (T-DM1) vs 30.8% (control) (P<0.001).
- Time to symptom progression was delayed in T-DM1 group.

Criticisms

- Open-label design may introduce bias.
- Certain subgroups had less definitive benefits.

Funding

Funded by F. Hoffmann–La Roche/Genentech, a member of the Roche Group.

Further Reading