Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 532
© 2008 American Society of Clinical Oncology

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Abstract

NCIC-CTG MA14 Trial: Tamoxifen (tam) vs. tam + octreotide (oct) for adjuvant treatment of stage I or II postmenopausal breast cancer

McGill University, Jewish General Hospital, Montreal, QC, Canada; National Cancer Institute of Canada, Kingston, ON, Canada; Odette Cancer Centre, Toronto, ON, Canada; SMDC Cancer Center, Duluth, MN; Thunder Bay Regional Health Sciences Centre, Thunder Bay, ON, Canada; London Regional Cancer Program, London, ON, Canada; British Columbia Cancer Agency, Fraser Valley Centre, Surrey, BC, Canada; Juravinski Cancer Centre at Hamilton Health Science, Hamilton, ON, Canada

532

Background: Our preclinical data (Cancer Res. 54:6334,1994) suggested mechanisms involving insulin/IGF physiology by which a somatostatin analogue + tam combination might be superior to tam alone for adjuvant BC therapy. Methods: In 1996, we began a Phase 3 trial randomizing stage I or II postmenopausal BC patients to tam 20mg daily for 5 yr with or without oct (monthly 90mg depot injection) for 5 yr, later reduced to 2 yr due to concern regarding cholelithiasis. Stratification factors included adjuvant chemotherapy, axillary nodal status, and ER status. Primary endpoint was event-free survival (EFS), defined as time from randomization to recurrence, second malignancy, or death due to any cause, assessed with the adjusted log-rank test statistic and an adjusted step-wise forward Cox regression. Objectives included studies of relevant biomarkers in relation to treatment and outcomes. Results: 667 women were accrued (333 to tam, 334 to tam +oct), with a median follow-up of 7.9 years and 220 events: 112 on tam (50.9%) and 108 on tam+oct (49.1%). The log-rank p=0.62, and the hazard ratio for tam+oct to tam is 0.93 (95% CI 0.71 to 1.22). Of 135 recurrences, 72 were on tam and 63 on tam+oct. As predicted by our lab model (Endocrinology. 130:3395,1992), there was a decline in mean IGF-1 on tam (baseline to nadir 121 to 75.3 ng/ml [p<0.0001]). On tam+oct this decline was from 121.2 to 61.2 (p<0.0001). On tam, a rise in c-peptide, 3.1 to 3.9 ng/ml (p<0.0001) was seen, while there was no significant change in c-peptide on tam+oct (3.3 to 3.4 ng/ml, p=0.22). Mean BMI increased significantly on tam (27.6 to 28.1, p=0.02), but not on tam +oct (28.0 to 27.7, p=0.20). In multivariate assessment, there was longer EFS for women <60 (p=0.01), T stage < T2 (p=0.004), N0 (p=0.01), and lower c-peptide (p<0.0001); lower BMI was associated with longer EFS (p<0.0001) in models that excluded c- peptide. Conclusions: No difference in EFS was seen between treatment arms, although there were differences in biomarkers. High c- peptide level was a strong negative prognostic factor, accounting for the adverse influence of obesity. Research is needed regarding the possibility that metabolically defined subsets of BC patients might benefit from oct+tam or other therapies that target insulin-IGF.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis

Abstract presentation from the 2008 ASCO Annual Meeting