ASCO 2014. Abstract LBA505. Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy (CT) to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer: An international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance).
Halle C. F. Moore, Joseph M. Unger, Kelly-Anne Phillips, Frances M. Boyle, Erika Hitre, David James Porter, Prudence A. Francis, Lori M. Minasian, Richard D. Gelber, Lori J. Goldstein, Henry Leonidas Gomez, Carlos Vallejos, Ann H. Partridge, Shaker R. Dakhil, Silvana Martino, William E. Barlow, Carol J. Fabian, Frank L. Meyskens, Gabriel N. Hortobagyi, Kathy S. Albain; Cleveland Clinic, Cleveland, OH; SWOG Statistical Center, Seattle, WA; Peter MacCallum Cancer Center, Melbourne, Australia; The Mater Hospital, Sydney, Australia; National Institute of Oncology, Budapest, Hungary; Department of Oncology, Auckland City Hospital, Auckland, New Zealand; Peter MacCallum Cancer Centre, East Melbourne, Australia; National Cancer Institute, Bethesda, MD; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA; Fox Chase Cancer Center, Philadelphia, PA; Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru; ONCOSALUD, Lima, Peru; Dana-Farber Cancer Institute, Boston, MA; Wichita Community Clinical Oncology Program, Wichita, KS; The Angeles Clinic and Research Institute, Santa Monica, CA; Cancer Research and Biostatistics, Seattle, WA; University of Kansas Medical Center, Kansas City, KS; Chao Family Comprehensive Cancer Center, Orange, CA; The University of Texas MD Anderson Cancer Center, Houston, TX; Loyola University Medical Center, Maywood, IL
Background: Premature ovarian failure (POF) is a common toxicity of CT. Risk depends on type and amount of CT, age, and perhaps ovarian cycling at the time of CT. POEMS is a SWOG coordinated phase III randomized study to evaluate whether LHRH analog administration with CT for early-stage breast cancer (BC) would reduce POF.
Methods: Premenopausal patients (PT) age<50 with stage I-IIIA ER/PR-negative BC to be treated with CT were randomized to receive standard cyclophosphamide-containing CT with or without monthly goserelin (GN) 3.6 mg SQ starting 1 week prior to the first CT dose. The primary endpoint is 2-year POF, defined as amenorrhea for the prior 6 months and post-menopausal FSH. Other endpoints include pregnancies and survival. Endpoints were analyzed in multivariable regression adjusting for stratification factors (age and CT regimen).
Results: Between 2/04 and 5/11, 257 PT enrolled. Among 218 evaluable PT, 62% had complete primary endpoint data. Dropouts (n=83) were mostly due to deaths (n=14) or lack of FSH data. There was no strong evidence of informative missing data by arm according to stratification factors (p>.05). POF rates were 22% in the standard arm and 8% in the GN arm (OR=0.30, 95% CI: 0.10-0.87, p=.03 [unadjusted analysis]; OR= 0.36, 95%CI: 0.11-1.14, p=0.08 [adjusted logistic regression analysis]). In a sensitivity analysis defining 2-year POF more liberally as either amenorrhea or elevated FSH, 45% in the standard arm and 20% in the GN arm had POF (OR=0.29, 95% CI: 0.12-0.70, p=.006). There were 13 pregnancies in the standard arm and 22 in the GN arm (OR=2.22, 95% CI: 1.00-4.92, p=.05). DFS and OS were better in the GN arm (Cox regression, including stage: HR=0.49, 95% CI: 0.24-0.97, p=.04; HR= 0.43, 95% CI: 0.18-1.00, p=.05, respectively).
Conclusions: LHRH analog administration with CT was associated with less POF and more pregnancies. In an exploratory analysis, GN use in premenopausal ER-negative BC was associated with improved DFS and OS.
- Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy (CT) to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer: An international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance). H.C.F Moore et al. J Clin Oncol 32:5s, 2014 (suppl; abstr LBA505)
- Randomized comparison of adjuvant aromatase inhibitor (AI) exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): Joint analysis of IBCSG TEXT and SOFT trials. O Pagani et al. J Clin Oncol 32:5s, 2014 (suppl; abstr LBA1)