The standard of care for patients diagnosed with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer is treatment with cytotoxic chemotherapy in combination with trastuzumab and pertuzumab. Although this combination is considered highly effective, chemotherapy-associated toxicity is a persistent clinical challenge. Sara Hurvitz at the University of California, Los Angeles, provided expertise on the KRISTINE/TRIO-021 trial that investigated neoadjuvant trastuzumab emtansine when combined with pertuzumab and compared it with the standard treatment regimen of docetaxel + carboplatin + trastuzumab + pertuzumab (TCHP).
It remains unclear whether in patients with premenopausal early breast cancer if there is an association of trastuzumab emtansine + pertuzumab and TCHP with treatment-related amenorrhea.
At study entry, all premenopausal patients with a documented menstrual period within 3 months of randomization were assessed for the absence or presence of treatment-related amenorrhea, characterized as cessation of menstruation for more than 12 months in the absence of treatment with ovarian suppression or other interventions that can induce amenorrhea. Follow-up evaluation of patients was conducted, from the time of study entry through the 3-year follow-up period after surgery.
Of the total 444 patients enrolled in the study, 239 premenopausal women were evaluated in this exploratory analysis to determine the association between trastuzumab emtansine + pertuzumab and treatment-related amenorrhea. The median age was 40 years (range, 22-53 years) for those treated with TCHP and 42.5 years (range, 23-52 years) for those treated with trastuzumab emtansine + pertuzumab.
Treatment-related amenorrhea occurred in 55% of patients treated with TCHP compared with 30% of patients treated with trastuzumab emtansine + pertuzumab. Treatment-related amenorrhea occurred in 62% with TCHP compared with 35% for trastuzumab emtansine + pertuzumab, in patients with hormone receptor–positive early breast cancer. Treatment-related amenorrhea was observed in 42% with TCHP versus 21% with trastuzumab emtansine + pertuzumab in those with hormone receptor early breast cancer.
In the trastuzumab emtansine + pertuzumab arm, treatment-related amenorrhea was observed in 38% of patients treated with standard adjuvant chemotherapy compared with 28% of patients who were not.
For women aged ≤40 years, treatment-related amenorrhea was 38% with TCHP compared with 17% with trastuzumab emtansine + pertuzumab. For women aged >40 years, treatment-related amenorrhea was observed in 74% of patients treated with TCHP compared with 39% of those treated with trastuzumab emtansine + pertuzumab.
The authors concluded that treatment-related amenorrhea with standard TCHP occurred at a rate that was nearly double that observed with trastuzumab emtansine + pertuzumab; this implies that to preserve gonadal function through lessened exposure to gonadal toxicity, targeted chemotherapy with an antibody–drug conjugate regimen may be advisable.
In women aged >40 years, the percentage of treatment-related amenorrhea cases were higher for each treatment arm. Nevertheless, in each age-group, trastuzumab emtansine + pertuzumab was associated with a lower rate of treatment-related amenorrhea.
Source: Hurvitz SA, Fresco R, Afenjar K, et al. Treatment-related amenorrhea with T-DM1 plus pertuzumab (KP) is lower than with docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) in the phase III neoadjuvant KRISTINE trial. Presented at: 2020 San Antonio Breast Cancer Symposium, December 8-11, 2020. Abstract PD12-06.