HER2-positive breast cancer represents 15%-20% of all breast cancers. The prognosis of this subtype significantly improved with the introduction of trastuzumab, a recombinant monoclonal antibody targeting HER2. Dual anti-HER2 blockade with trastuzumab and pertuzumab resulted in improved outcomes in patients with high-risk early breast cancer. In the adjuvant phase III APHINITY trial, the addition of pertuzumab to trastuzumab and chemotherapy improved invasive disease-free survival (DFS) in patients with node-positive disease, independently from hormone receptor (HR) status.1 The combination of trastuzumab plus lapatinib improved pathological complete response in several neoadjuvant trials, but no significant differences were seen in long-term outcomes.2 The ALTTO trial evaluated the role of dual HER2-blockade with trastuzumab plus lapatinib in the adjuvant setting.3
METHODS
The prospective, open-label, multi-centre, phase III ALTTO trial enrolled 8,381 patients with early HER2-positive breast cancer. These patients were randomised to receive adjuvant chemotherapy and trastuzumab alone, lapatinib alone, trastuzumab plus lapatinib, or trastuzumab followed by lapatinib. The primary endpoint was DFS and secondary endpoints included overall survival (OS), time to distant recurrence and safety.
RESULTS
The lapatinib-alone group was inferior and prematurely closed. Therefore, a total of 6,281 patients have been included in the final efficacy analysis. Patient and tumour characteristics were well-balanced among the three groups. At a median follow-up of 9.8 years, the addition of lapatinib to trastuzumab did not improve DFS nor OS. The 10-year DFS was 77% in the trastuzumab-alone group, 79% in the trastuzumab plus lapatinib group, and 79% in the trastuzumab followed by lapatinib group, and the 10-year OS was 87%, 89%, and 89%, respectively. No subgroup differences (HR status, nodal status) were observed between groups. The incidence of central nervous system (CNS) recurrence as the first recurrence was similar among groups, with a 2% incidence of CNS recurrence in each group. The incidence of primary cardiac events was low, with an overall incidence of 0.92% in the trastuzumab-alone group, 1.0% in the trastuzumab plus lapatinib group, and 0.53% in the trastuzumab followed by lapatinib group.
CONCLUSIONS
No significant improvement was seen in DFS in patients treated with adjuvant dual anti-HER2 blockade with trastuzumab plus lapatinib compared to trastuzumab alone in the final analysis of the ALTTO trial.
References
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