Extended adjuvant aromatase inhibition after sequential endocrine therapy (DATA): a randomised, phase 3 trial

Tjan‐Heijnen, Vivianne C. G.; Hellemond, Irene E G van; Peer, Petronella G. M.; Swinkels, Astrid; Smorenburg, Carolien H.; Sangen, M.J.C. van der; Kroep, Judith R.; Graaf, Hiltje de; Honkoop, Aafke H.; Erdkamp, Frans; Berkmortel, Franchette W P J van den; Boer, Maaike de; Roos, W; Linn, Sabine C.; Imholz, Alexander L.T.; Seynaeve, Caroline; Kitzen, Jos; Strobbe, L.J.A.; Kouwenhoven, E.A.; Dalen, T van; Overbeeke, Adriaan J van; Nuytinck, J. K. S.; Arntz, I.E.; Blaisse, Reinoud J B; Stockmann, H. B. A. C.; Nijhuis, P.H.A.; Veldhuis, Gerrit-Jan; Mastboom, W.J.B.; Riel, J.M.G.H. van; Dam, Johan Hygum; Boer, Marien O den; Agterof, Mariette J; Roos, Marnix A.J. de; Roumen, R. M. H.; Hoeven, J.J.M. van der; Beeker, Aart; Koelemij, R.; Bochove, Aart van; Madretsma, G. S.; Siemerink, E.; Guicherit, Onno R.; Vos, Allert H.; Nieuwenhuijzen, Grard A. P.; Kehrer, Diederik F.S.; Valster, F.A.A.; Tanis, Bea C.; Voorthuizen, Theo van; Velden, Ankie M.T. van der; Hellingman, R.A.; Vree, R.; Rossum-Schornagel, Q. van; Terwogt, Jetske M. Meerum; Leeuwen-Breuk, W.G. van; Haasjes, Janny G.; Schoonhoven, Marjan A. Davidis-van; Vriens, Eline; Jagers, M.; Müller, E; Schiphorst, P. P.; Groeningen, C.J. van; Dijk, Maarten A van; Vliet, Esmée J. van; Schepers, Eva; Merkus, J. W. S.; Diemen, N. G. J. Van; Doorn, R.C. van; Bosscha, K.; Toom, R. Den; Velden, P.C. van der; Rossum, C.T.A.M. van; Oosterkamp, Hendrika M.; Hillegersberg, Richard van; Jas, B.; Weernink, E. E. M.; Ketel, J.M.A.; Jansen, JP; Maring, John K.; Govaert, Marc J. P. M.; Kamm, Y.J.L.; Vleugel, Marije M.; Hovenga, Sjoerd; Boer, J. de; Potthoff, H.; Sommeijer, Dirkje W.; Dulken, Eric J van

doi:10.1016/s1470-2045(17)30600-9

Cited by 126 publications

(96 citation statements)

References 25 publications

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“…The 5‐year survival rates were calculated starting at randomization. About 42% of the women included in the DATA study were aged 60 years and above . Of note, to overcome the influence of age (and its associated comorbidities) on survival in the analyses, we selected only those definitely postmenopausal patients who were within the same range of age (45–57 years) as the women with CIOFF.…”

Section: Methodsmentioning

confidence: 99%

“…The phase III DATA study assesses the impact of different durations of adjuvant anastrozole on survival after prior tamoxifen in postmenopausal women with hormone receptor‐positive early breast cancer . Women with CIOFF were also eligible.…”

Section: Introductionmentioning

confidence: 99%

“…4,6,7 The phase III DATA study assesses the impact of different durations of adjuvant anastrozole on survival after prior tamoxifen in postmenopausal women with hormone receptor-positive early breast cancer. 8 Women with CIOFF were also eligible. A recent analysis of the DATA study showed biochemical OFR in 12.4% of women with CIOFF at 30 months after randomization.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of anastrozole after tamoxifen in early breast cancer patients with chemotherapy‐induced ovarian function failure

Hellemond

Vriens

Peer³

et al. 2019

Intl Journal of Cancer

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The DATA study (NCT00301457) compared 6 and 3 years of anastrozole in postmenopausal women with hormone receptor‐positive early breast cancer after 2–3 years of tamoxifen. Patients with chemotherapy‐induced ovarian function failure (CIOFF) were also eligible, but could be at risk of ovarian function recovery (OFR). The current analysis compared the survival of women with CIOFF with definitely postmenopausal women and examined the influence of OFR on survival. Therefore, we selected patients from the DATA study aged 45–57 years at randomization who had received (neo)adjuvant chemotherapy. They were classified by reversibility of postmenopausal status: possibly reversible in case of CIOFF ( n = 395) versus definitely postmenopausal ( n = 261). The former were monitored by E2 measurements for OFR. The occurrence of OFR was incorporated as a time‐dependent covariate in a Cox‐regression model for calculating the hazard ratio (HR). We used the landmark method to calculate residual 5‐year survival rates. When comparing CIOFF women with definitely postmenopausal women, the survival was not different. Among CIOFF women with available E2 follow‐up values ( n = 329), experiencing OFR ( n = 39) had an unfavorable impact on distant recurrence‐free survival (HR 2.27 [95% confidence interval [CI] 0.98–5.25; p = 0.05] and overall survival (HR 2.61 [95% CI 1.11–6.13; p = 0.03]). After adjusting for tumor features, the HRs became 2.11 (95% CI 0.89–5.02; p = 0.09) and 2.24 (95% CI 0.92–5.45; p = 0.07), respectively. The residual 5‐year rate for distant recurrence‐free survival was 76.9% for women with OFR and 92.1% for women without OFR, and for 5‐year overall survival 80.8% and 94.4%, respectively. Women with CIOFF receiving anastrozole may be at increased risk of disease recurrence if experiencing OFR.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy of anastrozole after tamoxifen in early breast cancer patients with chemotherapy‐induced ovarian function failure

Hellemond

Vriens

Peer³

et al. 2019

Intl Journal of Cancer

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“…The DATA study (NCT00301457) is a prospective randomised phase III study in which postmenopausal women with early breast cancer were assigned to different durations of anastrozole therapy (6 vs. 3 years) after 2 to 3 years of tamoxifen as adjuvant endocrine therapy. 7 The study included a total of 1860 eligible postmenopausal women from June 2006 till August 2009. The protocol of the bone-health side study was approved by the Medical Ethical Committee of the Radboud University Nijmegen at November 22, 2009.…”

Section: Methodsmentioning

confidence: 99%

“…5,6 The DATA study investigated the efficacy of 6 vs. 3 years of adjuvant anastrozole after a prior treatment with 2-3 years of tamoxifen in postmenopausal women with hormone receptor positive early breast cancer. 7 We pre-planned a side study to evaluate patterns of care considering bone health in these women, and the trend of BMD over time during and after cessation of anastrozole treatment. These research questions are addressed in the current report.…”

Section: Introductionmentioning

confidence: 99%

Assessment and management of bone health in women with early breast cancer receiving endocrine treatment in the DATA study

Hellemond

Smorenburg

Peer³

et al. 2019

Intl Journal of Cancer

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The phase III DATA study investigates the efficacy of adjuvant anastrozole (6 vs. 3 year) in postmenopausal women with breast cancer previously treated with 2–3 years of tamoxifen. This planned side‐study assessed patterns of care regarding detection and treatment of osteopenia/osteoporosis, and trends in bone mineral density (BMD) during and after therapy. We registered all BMD measurements and bisphosphonate‐use. Time to osteopenia/osteoporosis was analysed by Kaplan Meier methodology. For the trend in T‐scores we used linear mixed models with random patients effects. Of 1860 eligible DATA patients, 910 (48.9%) had a baseline BMD measurement. Among patients with a normal baseline BMD (n = 417), osteopenia was observed in 53.5% and 55.4% in the 6‐ and 3‐year group respectively (p = 0.18), during follow‐up. Only two patients (3‐year group) developed osteoporosis. Of the patients with osteopenia at baseline (n = 408), 24.4% and 20.4% developed osteoporosis respectively (p = 0.89). Three years after randomisation 18.3% and 18.2% used bisphosphonates in the 6‐ and 3‐year groups respectively and 6 years after randomisation this was 23.7% and 20.9% respectively (p = 0.90) of which the majority used oral bisphosphonates. The yearly mean BMD‐change during anastrozole in the lumbar spine showed a T‐score decline of 0.075. After bisphosphonate addition the decline became less prominent (0.047 (p < 0.001)) and after anastrozole cessation, while continuing bisphosphonates, the mean BMD yearly increased (0.047 (p < 0.001)). In conclusion, extended anastrozole therapy was not associated with a higher incidence of osteoporosis. Anastrozole‐use was associated with a BMD decrease; however, the decline was modest and partially reversible after anastrozole cessation.

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Association of Industry and Academic Sponsorship With Negative Phase 3 Oncology Trials and Reported Outcomes on Participant Survival

2019

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Key Points Question Does an association exist between the sponsorship and conduct of phase 3 randomized clinical trials for cancer drugs despite negative or absent phase 2 trials for the drug, and does an association exist for overall patient survival and such phase 3 trials? Findings This analysis of 67 studies found that both industry and academia conducted negative phase 3 trials of cancer drugs. No association was found between trial sponsorship and lack of a positive phase 2 trial; there was no association with patient overall survival, although the survival hazard ratio was greater than 1 for 37% of such trials. Meaning Phase 3 trials conducted without supporting phase 2 trial evidence risks loss of resources owing to trial failure and may be associated with decreased patient survival.

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Extended adjuvant aromatase inhibition after sequential endocrine therapy (DATA): a randomised, phase 3 trial

Cited by 126 publications

References 25 publications

Efficacy of anastrozole after tamoxifen in early breast cancer patients with chemotherapy‐induced ovarian function failure

Efficacy of anastrozole after tamoxifen in early breast cancer patients with chemotherapy‐induced ovarian function failure

Assessment and management of bone health in women with early breast cancer receiving endocrine treatment in the DATA study

Association of Industry and Academic Sponsorship With Negative Phase 3 Oncology Trials and Reported Outcomes on Participant Survival

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