Cyclophosphamide-Free Adjuvant Chemotherapy for Ovarian Protection in Young Women With Breast Cancer: A Randomized Phase 3 Trial.

Abstract

BACKGROUND:

Chemotherapy-induced premature menopause leads to some consequences, including infertility. We initiated this randomized phase III trial to determine whether a cyclophosphamide-free adjuvant chemotherapy regimen would increase the likelihood of menses resumption and improve survival outcomes.

METHODS:

Young women with operable estrogen receptor-positive HER2-negative breast cancer after definitive surgery were randomly assigned to receive adjuvant epirubicin and cyclophosphamidefollowed by weekly paclitaxel (EC-wP) or epirubicin and paclitaxel followed by weekly paclitaxel (EP-wP). All patients received at least 5-year adjuvant endocrine therapy after chemotherapy. Two coprimary endpoints were the rate of menstrual resumption at 12 months after chemotherapy and 5-year disease-free survival in the intention-to-treat population. This study is registered at ClinicalTrials.gov (NCT01026116). All statistical tests were 2-sided.

RESULTS:

Between January 2011 and December 2016, 521 patients (median age = 34 years; interquartile range = 31-38 years) were enrolled, with 261 in the EC-wP group and 260 in the EP-wP group. The rate of menstrual resumption at 12 months after chemotherapy was 48.3% in EC-wP (95% confidence interval [CI] = 42.2% to 54.3%) and 63.1% in EP-wP (95% CI = 57.2% to 68.9%), with an absolute difference of 14.8% (95% CI = 6.37% to 23.2%, P < .001). The posthoc exploratory analysis by patient-reported outcome questionnaires indicated that pregnancy might occur in fewer women in the EC-wP group than in the EP-wP group. At a median follow-up of 62 months, the 5-year disease-free survival was 78.3% (95% CI = 72.2% to 83.3%) in EC-wP and 84.7% (95% CI = 79.3% to 88.8%) in EP-wP (stratified log-rank P = .07). The safety data were consistent with the known safety profiles of relevant drugs.

CONCLUSIONS:

The cyclophosphamide-free chemotherapy regimen might be associated with a higher probability of menses resumption.

• Authors: Ke-Da Yu, Jing-Yu Ge, Xi-Yu Liu, Miao Mo, Min He, Zhi-Ming Shao, SPECTRUM Investigators
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 113 Issue 10 Pg. 1352-1359 (10 01 2021) ISSN: 1460-2105 [Electronic] United States
• PMID: 33822134 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press.

Chemical References

• Epirubicin
• Cyclophosphamide
• Paclitaxel

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Breast Neoplasms (drug therapy)
• Chemotherapy, Adjuvant
• Cyclophosphamide (adverse effects)
• Disease-Free Survival
• Epirubicin (adverse effects)
• Female
• Humans
• Paclitaxel (adverse effects)
• Pregnancy
• Treatment Outcome