Low-dose oral cyclophosphamide and methotrexate maintenance for hormone receptor-negative early breast cancer: International Breast Cancer Study Group Trial 22-00

Marco Colleoni, Kathryn P. Gray, Shari Gelber, I. Láng, Beat Thürlimann, Lorenzo Gianni, Ehtesham A. Abdi, Henry L. Gomez, Barbro K. Linderholm, Fabio Puglisi, Carlo Tondini, Elena Kralidis, Alexandru Eniu, Katia Cagossi, Daniel Rauch, Jacquie Chirgwin, Richard D. Gelber, Meredith M. Regan, Alan S. Coates, Karen N. PriceGiuseppe Viale, Aron Goldhirsch

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Purpose: To evaluate the benefit of low-dose cyclophosphamide and methotrexate (CM) maintenance, which previously demonstrated antitumor activity and few adverse effects in advanced breast cancer, in early breast cancer. Patients and Methods: International Breast Cancer Study Group (IBCSG) Trial 22-00, a randomized phase III clinical trial, enrolled 1,086 women (1,081 intent-to-treat) from November 2000 to December 2012. Women with estrogen receptor- and progesterone receptor-negative (< 10% positive cells by immunohistochemistry) early breast cancer any nodal and human epidermal growth factor receptor 2 status, were randomly assigned anytime between primary surgery and 56 days after the first day of last course of adjuvant chemotherapy to CM maintenance (cyclophosphamide 50 mg/day orally continuously and methotrexate 2.5 mg twice/day orally on days 1 and 2 of every week for 1 year) or to no CM. The primary end point was disease-free survival (DFS), which included invasive recurrences, second (breast and nonbreast) malignancies, and deaths. Results: After a median of 6.9 years of follow-up, DFS was not significantly better for patients assigned to CM maintenance compared with patients assigned to no CM, both overall (hazard ratio [HR], 0.84; 95% CI, 0.66 to 1.06; P = .14) and in triple-negative (TN) disease (n = 814; HR, 0.80; 95% CI, 0.60 to 1.06). Patients with TN, node-positive disease had a nonstatistically significant reduced HR (n = 340; HR, 0.72; 95% CI, 0.49 to 1.05). Seventy-one (13%) of 542 patients assigned to CM maintenance did not start CM. Of 473 patients who received at least one CM maintenance dose (including two patients assigned to no CM), 64 (14%) experienced a grade 3 or 4 treatment-related adverse event; elevated serum transaminases was the most frequently reported (7%), followed by leukopenia (2%). Conclusion: CM maintenance did not produce a significant reduction in DFS events in hormone receptor-negative early breast cancer. The trend toward benefit observed in the TN, node-positive subgroup supports additional exploration of this strategy in the TN, higher-risk population.

Original languageEnglish
Pages (from-to)3400-3408
Number of pages9
JournalJournal of Clinical Oncology
Volume34
Issue number28
DOIs
Publication statusPublished - Oct 1 2016

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Colleoni, M., Gray, K. P., Gelber, S., Láng, I., Thürlimann, B., Gianni, L., Abdi, E. A., Gomez, H. L., Linderholm, B. K., Puglisi, F., Tondini, C., Kralidis, E., Eniu, A., Cagossi, K., Rauch, D., Chirgwin, J., Gelber, R. D., Regan, M. M., Coates, A. S., ... Goldhirsch, A. (2016). Low-dose oral cyclophosphamide and methotrexate maintenance for hormone receptor-negative early breast cancer: International Breast Cancer Study Group Trial 22-00. Journal of Clinical Oncology, 34(28), 3400-3408. https://doi.org/10.1200/JCO.2015.65.6595