Lapatinib With Trastuzumab and Aromatase Inhibition Improves PFS in HER2-positive Breast Cancer

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The treatments arms that received lapatinib, however, had a higher AE rate than the TRAS+AI arm.
The treatments arms that received lapatinib, however, had a higher AE rate than the TRAS+AI arm.

Lapatinib (LAP) with trastuzumab (TRAS) plus an aromatase inhibitor (AI) may prolong progression-free survival (PFS) among women with HER2-positive, hormone receptor–positive metastatic breast cancer (MBC) compared with TRAS plus an AI, according to a study published in the Journal of Clinical Oncology.1

For the phase 3 ALTERNATIVE study ( Identifier: NCT01160211), researchers randomly assigned 355 patients to 1 of 3 treatment arms: LAP+TRAS+AI, TRAS+AI, or LAP+AI (patients received investigator's choice of oral letrozole or anastrozole for the AI).

Patients in the LAP+TRAS+AI arm had a superior median PFS of 11.0 months compared with 5.7 months in the TRAS+AI arm (hazard ratio [HR], 0.62; 95% CI, 0.45-0.88; P = .0064); this PFS benefit was observed across all analyzed subgroups.

Patients treated with LAP+TRAS+AI also had an improved overall response rate (ORR) compared with patients in the TRAS+AI and LAP+AI groups (31.7% vs 13.7% and 18.6%, respectively), as well as clinical benefit rate (41% vs 31% and 33%).

The median PFS for LAP+AI vs TRAS+AI was 8.3 months vs 5.7 months, respectively (HR, 0.71; 95% CI, 0.51-0.98; P = .0361).

The most frequently reported adverse events (AEs) across the 3 treatment arms included diarrhea, rash, nausea, and paronychia, most of which were grade 1 or 2.

The treatments arms that received LAP, however, had a higher AE rate than the TRAS+AI arm.

The authors concluded that “this combination can potentially offer an effective and well-tolerated, chemotherapy-sparing alternative treatment regimen for patients for whom chemotherapy is not intended.”


  1. Johnston SR, Hegg R, Im SA, et al. Phase III, randomized study of dual human epidermal growth factor receptor 2 (HER2) blockade with lapatinib plus trastuzumab in combination with an aromatase inhibitor in postmenopausal women with HER2-positive, hormone receptor-positive metastatic breast cancer: ALTERNATIVE. J Clin Oncol. 2017 Dec 15. doi: 10.1200/JCO.2017.74.7824 [Epub ahead of print]

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