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

• DOI: 10.1007/s10549-021-06267-8
• Publication Date: 2021-06-12T18:02:22Z
• Authors: Kathryn J. Ruddy; Yue Zheng; Nabihah Tayob; Jiani Hu; Chau T. Dang; Denise A. Yardley; Steven J. Isakoff; Vicente V. Valero; Meredith G. Faggen; Therese M. Mulvey; Ron Bose; Tal Sella; Douglas J. Weckstein; Antonio C. Wolff; Katherine E. Reed...; Hope S. Rugo; Bhuvaneswari Rama...; Dan S. Zuckerman; Lowell L. Hart; Vijayakrishna K. ...; Michael Constantine; Kit L. Cheng; Frederick M. Bric...; Bryan P. Schneider; A. Merrill Garrett; P. Kelly Marcom; Kathy S. Albain; Patricia A. DeFusco; Nadine M. Tung; Blair M. Ardman; Rita Nanda; Rachel C. Jankowitz; Mothaffar Rimawi; Vandana Abramson; Paula R. Pohlmann; Catherine Van Poznak; Andres Forero-Torres; Minetta C. Liu; Shoshana Rosenberg; Michelle K. DeMeo; Harold J. Burstein; Eric P. Winer; Ian E. Krop; Ann H. Partridge; Sara M. Tolaney
• Keywords: Adult; 0301 basic medicine; Paclitaxel; Receptor, ErbB-2; Breast Neoplasms; Middle Aged; Trastuzumab; Ado-Trastuzumab Emtansine; 3. Good health; Young Adult; 03 medical and health sciences; Antineoplastic Combined Chemotherapy Protocols; Humans; Female; Maytansine; Amenorrhea

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).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/m2 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.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).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.