Lambertini M, et al. - Researchers assessed treatment-related amenorrhea (TRA) rates following one year of treatment with trastuzumab, lapatinib, their sequence, or their combination in premenopausal patients with human epidermal growth factor receptor 2 (HER2)–positive and –negative early breast cancer. They also investigated the impact of TRA on disease-free survival (DFS) and overall survival (OS). They found no association between TRA rate and type of anti-HER2 treatment in this unplanned analysis. In premenopausal hormone receptor–positive/HER2-positive early breast cancer patients, an association of TRA with statistically significant survival benefits was observed.

Methods

• Researchers randomized (1:1:1:1) HER2-positive early breast cancer patients to receive one year of trastuzumab, lapatinib, their sequence, or their combination in the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (BIG 2-06) phase 3 trial.
• They collected menopausal status in all patients at random assignment and at week 37 visit.
• To account for guarantee-time bias, they used landmark and time-dependent modeling; all statistical tests were two-sided.

Results

• This study included 2,862 premenopausal women with median age 43 (interquartile range=38–47) years, of whom 1,679 (58.7%) had hormone receptor–positive disease.
• The estimated TRA rates in the trastuzumab (72.6%), lapatinib (74.0%), trastuzumab-then-lapatinib (72.1%), and trastuzumab+lapatinib (74.8%) arms (P=.64) were similar.
• For hormone receptor–positive patients, statistically significantly better DFS (adjusted hazard ratio [aHR] = 0.58, 95% confidence interval [CI] = 0.45 to 0.76) and OS (aHR = 0.63, 95% CI = 0.40 to 0.99) were reported in the TRA cohort vs the no TRA cohort.
• They reported no difference in hormone receptor–negative patients.