Title
Concurrent and sequential initiation of ovarian function suppression with chemotherapy in premenopausal women with endocrine-responsive early breast cancer: An exploratory analysis of TEXT and SOFT
Date Issued
01 September 2017
Access level
open access
Resource Type
journal article
Author(s)
Regan M.M.
Walley B.A.
Francis P.A.
Fleming G.F.
Láng I.
Colleoni M.
Tondini C.
Pinotti G.
Salim M.
Spazzapan S.
Parmar V.
Ruhstaller T.
Abdi E.A.
Gelber R.D.
Coates A.S.
Goldhirsch A.
Pagani O.
Publisher(s)
Oxford University Press
Abstract
Background: Recent breast cancer treatment guidelines recommend that higher-risk premenopausal patients should receive ovarian function suppression (OFS) as part of adjuvant endocrine therapy. If chemotherapy is also given, it is uncertain whether to select concurrent or sequential OFS initiation. Design and methods: We analyzed 1872 patients enrolled in the randomized phase III TEXT and SOFT trials who received adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer and upon randomization to an OFScontaining adjuvant endocrine therapy, initiated gonadotropin-releasing-hormone-agonist triptorelin. Breast cancer-free interval (BCFI) was compared between patients who received OFS concurrently with chemotherapy in TEXT (n=1242) versus sequentially post-chemotherapy in SOFT (n=630). Because timing of trial enrollment relative to adjuvant chemotherapy differed, we implemented landmark analysis re-defining BCFI beginning 1 year after final dose of chemotherapy (median, 15.5 and 8.1 months from enrollment to landmark in TEXT and SOFT, respectively). As a non-randomized treatment comparison, we implemented comparative-effectiveness propensity score methodology with weighted Cox modeling. Results: Distributions of several clinico-pathologic characteristics differed between groups. Patients who were premenopausal post-chemotherapy in SOFT were younger on average. The median duration of adjuvant chemotherapy was 18 weeks in both groups. There were 231 (12%) BC events after post-landmark median follow-up of about 5 years. Concurrent use of triptorelin with chemotherapy was not associated with a significant difference in post-landmark BCFI compared with sequential triptorelin post-chemotherapy, either in the overall population (HR=1.11, 95% CI 0.72-1.72; P=0.72; 4-year BCFI 89% in both groups), or in the subgroup of 692 women < 40 years at diagnosis (HR=1.13, 95% CI 0.69-1.84) who are less likely to develop chemotherapy-induced amenorrhea. Conclusion: Based on comparative-effectiveness modeling of TEXT and SOFT after about 5 years median follow-up, with limited statistical power especially for the subgroup < 40 years, neither detrimental nor beneficial effect of concurrent administration of OFS with chemotherapy on the efficacy of adjuvant therapy that includes chemotherapy was detected.
Start page
2225
End page
2232
Volume
28
Issue
9
Language
English
OCDE Knowledge area
Obstetricia, Ginecología Patología Oncología
Scopus EID
2-s2.0-85029878235
PubMed ID
Source
Annals of Oncology
ISSN of the container
09237534
Sponsor(s)
TEXT and SOFT received financial support for trial conduct from Pfizer, the IBCSG and the US National Cancer Institute at the National Institutes of Health (NIH). Pfizer and Ipsen provided drug supply. The pharmaceutical companies have no role in the reporting or interpretation of the trials, other than a minority representation on the Steering Committee. Support for the coordinating group, IBCSG: Frontier Science and Technology Research Foundation [no grant number], Swiss Group for Clinical Cancer Research [SAKK; no grant number], Cancer Research Switzerland/Oncosuisse [no grant number], the Foundation for Clinical Cancer Research of Eastern Switzerland [OSKK; no grant number], US National Institutes of Health [grant number CA075362], Breast Cancer Research Foundation [BCRF; grant number 16-185]. Grant support of cooperative groups: Australia and New Zealand Breast Cancer Trials Group [National Health and Medical Research Council grant numbers 351161, 510788 and 1105058]; SWOG [US National Institutes of Health grant number CA32102]; Alliance for Clinical Trials in Oncology [US National Institutes of Health grant number CA180821]; ECOG-ACRIN Cancer Research Group [US National Institutes of Health grant numbers CA21115, CA16116]; NSABP/NRG Oncology [US National Institutes of Health grant numbers U10-CA12027, U10-CA69651, U10-CA37377, U10-CA69974]; NCIC-CTG [US National Institutes of Health grant number CA077202; and Canadian Cancer Society Research Institute grant numbers 015469, 021039]; ICR-CTSU on behalf of the National Cancer Research Institute Breast Clinical Studies Group United Kingdom (NCRI-BCSG—ICR-CTSU Partnership) [Cancer Research UK grant numbers CRUKE/03/022, CRUKE/03/023, A15955; National Institute for Health Research/Institute of Cancer Research Biomedical Research Centre (no grant number); National Institute for Health/Cambridge Biomedical Research Centre (no grant number)].
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