The following article features coverage from the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

When combined with an aromatase inhibitor (AI), dual HER2 blockade with trastuzumab (T) and lapatinib (L) shows superior progression-free survival (PFS) compared with lapatinib or trastuzumab alone in postmenopausal women with HER2-positive (HER+), hormone receptor-positive (HR+) breast cancer, according to data presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.1

The study was presented by William J. Gradishar, MD, of Northwestern University in Chicago, Illinois.

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ALTERNATIVE was a phase 3 study in which women were randomized in 1:1:1 to receive T + L (120 patients), T (117 patients), or L (120 patients). All patients received investigator’s choice of an AI.

Postmenopausal women enrolled in the study had HER2+, HR+ metastatic breast cancer (MBC), which progressed on first-line trastuzumab plus chemotherapy. Patients were excluded if they were candidates for chemotherapy.  

When given in combination with T, L was dosed at 1000 mg/day; when given alone, the dose was higher — 1500 mg/day.

Of 369 women enrolled in the study, data were presented for 355 women. For the primary endpoint, which evaluated the superiority of T + L + AI vs T + AI, median PFS was 11 months for patients on T + L and 5.7 months for patients on T. With a hazard ratio of 0.62, the combination of T + L + AI was superior to T + AI (P = .0064).

Objective response rate was also higher for the dual HER2 blockade: 31.7% for T + L + AI, 13.7% for T + AI, and 18.6% for L + AI. 

Survival data are not yet mature.

The most common adverse events were (T + L + AI vs T + AI vs L + AI): diarrhea (69% vs 9% vs 51%), rash (36% vs 2% vs 28%), nausea (22% vs 9% vs 22%), and paronychia (30% vs 0% vs 15%).

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On-treatment death rates were 3% for T + L + AI, 4% for T + AI, and 5% for L + AI.

Data from ALTERNATIVE suggest that dual HER2 blockade has the potential to offer an effective chemotherapy-sparing option in a subgroup of patients with HER+ HR+ MBC without aggressive disease and who are not candidates for chemotherapy, Dr Gradishar noted.

Read more of Cancer Therapy Advisor‘s coverage of the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting by visiting the conference page.


  1. Gradishar WJ, Hegg R, Im SA, et al. Phase II study of lapatinib (L) plus trastuzumab (T) and an aromatase inhibitor (AI) vs T + AI vs L + AI in postmenopausal women (PMW) with HER2+, HR+, metastatic breast cancer (MBC): ALTERNATIVE. J Clin Oncol. 2017;35(suppl; abstr 1004).