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

Breast Cancer Res Treat. 2021 Aug;189(1):103-110. doi: 10.1007/s10549-021-06267-8. Epub 2021 Jun 12.

Abstract

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/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.

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.

Keywords: Breast cancer; Chemotherapy; Fertility; Premenopausal.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Ado-Trastuzumab Emtansine / adverse effects
  • Adult
  • Amenorrhea / chemically induced
  • Amenorrhea / epidemiology
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Breast Neoplasms* / drug therapy
  • Female
  • Humans
  • Maytansine* / adverse effects
  • Middle Aged
  • Paclitaxel / adverse effects
  • Paclitaxel / therapeutic use
  • Receptor, ErbB-2 / genetics
  • Trastuzumab / adverse effects
  • Young Adult

Substances

  • Maytansine
  • Receptor, ErbB-2
  • Trastuzumab
  • Paclitaxel
  • Ado-Trastuzumab Emtansine