Chemotherapy-related amenorrhea (CRA) after adjuvant ado-trastuzumab emtansine (T-DM1) compared to paclitaxel in combination with trastuzumab (TH) (TBCRC033: ATEMPT Trial)

• Published in: Breast cancer research and treatment Vol. 189; no. 1; pp. 103 - 110
• Main Authors: Ruddy, Kathryn J., Zheng, Yue, Tayob, Nabihah, Hu, Jiani, Dang, Chau T., Yardley, Denise A., Isakoff, Steven J., Valero, Vicente V., Faggen, Meredith G., Mulvey, Therese M., Bose, Ron, Sella, Tal, Weckstein, Douglas J., Wolff, Antonio C., Reeder-Hayes, Katherine E., Rugo, Hope S., Ramaswamy, Bhuvaneswari, Zuckerman, Dan S., Hart, Lowell L., Gadi, Vijayakrishna K., Constantine, Michael, Cheng, Kit L., Briccetti, Frederick M., Schneider, Bryan P., Merrill Garrett, A., Kelly Marcom, P., Albain, Kathy S., DeFusco, Patricia A., Tung, Nadine M., Ardman, Blair M., Nanda, Rita, Jankowitz, Rachel C., Rimawi, Mothaffar, Abramson, Vandana, Pohlmann, Paula R., Van Poznak, Catherine, Forero-Torres, Andres, Liu, Minetta C., Rosenberg, Shoshana, DeMeo, Michelle K., Burstein, Harold J., Winer, Eric P., Krop, Ian E., Partridge, Ann H., Tolaney, Sara M.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2021; Springer Nature B.V
• Subjects: Ado-Trastuzumab Emtansine - adverse effects; Adult; Amenorrhea; Amenorrhea - chemically induced; Amenorrhea - epidemiology; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Breast cancer; Breast Neoplasms - drug therapy; Cancer research; Chemotherapy; Clinical Trial; ErbB-2 protein; Female; Gonadotropin-releasing hormone; Gonadotropins; Humans; Hysterectomy; Infertility; Maytansine - adverse effects; Medicine; Medicine & Public Health; Menopause; Menstruation; Middle Aged; Monoclonal antibodies; Oncology; Ovariectomy; Paclitaxel; Paclitaxel - adverse effects; Paclitaxel - therapeutic use; Pituitary (anterior); Receptor, ErbB-2 - genetics; Targeted cancer therapy; Toxicity; Trastuzumab; Trastuzumab - adverse effects; Young Adult; Premenopausal; Chemotherapy; Breast cancer; Fertility
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-021-06267-8

Purpose Chemotherapy-related amenorrhea (CRA) is a surrogate for ovarian toxicity and associated risk of infertility and premature menopause. Here, we compare CRA rate with paclitaxel (T)-trastuzumab (H) to that with ado-trastuzumab emtansine (T-DM1). Methods Patients with T1N0 HER2 + early-stage breast cancer (eBC) enrolled on the ATEMPT trial and were randomized 3:1 to T-DM1 3.6 mg/kg IV every (q) 3 weeks (w) × 17 vs. T 80 mg/m 2 with H IV qw × 12 (4 mg/kg load → 2 mg/kg), followed by H (6 mg/kg IV q3w × 13). Enrollees who self-reported as premenopausal were asked to complete menstrual surveys at baseline and every 6–12 months for 60 months. 18-month CRA (no periods reported during prior 6 months on 18-month survey) was the primary endpoint of this analysis. Results Of 512 ATEMPT enrollees, 123 who began protocol therapy and answered baseline and at least one follow-up menstrual survey were premenopausal at enrollment. 76 had menstrual data available at 18 months without having received a gonadotropin-releasing hormone agonist or undergone hysterectomy and/or oophorectomy. Median age was 45 (range 23–53) among 18 who had received TH and 46 (range 34–54) among 58 who had received T-DM1. The 18-month rate of CRA was 50% after TH and 24% after T-DM1 ( p  = 0.045). Conclusion Amenorrhea at 18 months was less likely in recipients of adjuvant T-DM1 than TH. Future studies are needed to understand how T-DM1 impacts risk of infertility and permanent menopause, and to assess amenorrhea rates when T-DM1 is administered after standard HER2-directed chemotherapy regimens.