Addition of zoledronic acid to neoadjuvant chemotherapy is not beneficial in patients with HER2-negative stage II/III breast cancer : 5-year survival analysis of the NEOZOTAC trial (BOOG 2010-01)
BACKGROUND: Adjuvant bisphosphonates are associated with improved breast cancer survival in postmenopausal patients. Addition of zoledronic acid (ZA) to neoadjuvant chemotherapy did not improve pathological complete response in the phase III NEOZOTAC trial. Here we report the results of the secondary endpoints, disease-free survival, (DFS) and overall survival (OS).
PATIENTS AND METHODS: Patients with HER2-negative, stage II/III breast cancer were randomized to receive the standard 6 cycles of neoadjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy with or without 4 mg intravenous (IV) ZA administered within 24 h of chemotherapy. This was repeated every 21 days for 6 cycles. Cox regression models were used to evaluate the effect of ZA and covariates on DFS and OS. Regression models were used to examine the association between insulin, glucose, insulin growth factor-1 (IGF-1) levels, and IGF-1 receptor (IGF-1R) expression with survival outcomes.
RESULTS: Two hundred forty-six women were eligible for inclusion. After a median follow-up of 6.4 years, OS for all patients was significantly worse for those who received ZA (HR 0.468, 95% CI 0.226-0.967, P = 0.040). DFS was not significantly different between the treatment arms (HR 0.656, 95% CI 0.371-1.160, P = 0.147). In a subgroup analysis of postmenopausal women, no significant difference in DFS or OS was found for those who received ZA compared with the control group (HR 0.464, 95% CI 0.176-1.222, P = 0.120; HR 0.539, 95% CI 0.228-1.273, P = 0.159, respectively). The subgroup analysis of premenopausal patients was not significantly different for DFS and OS ((HR 0.798, 95% CI 0.369-1.725, P = 0.565; HR 0.456, 95% CI 0.156-1.336, P = 0.152, respectively). Baseline IGF-1R expression was not significantly associated with DFS or OS. In a predefined additional study, lower serum levels of insulin were associated with improved DFS (HR 1.025, 95% CI 1.005-1.045, P = 0.014).
CONCLUSIONS: Our results suggest that ZA in combination with neoadjuvant chemotherapy was associated with a worse OS in breast cancer (both pre- and postmenopausal patients). However, in a subgroup analysis of postmenopausal patients, ZA treatment was not associated with DFS or OS. Also, DFS was not significantly different between both groups. IGF-1R expression in tumor tissue before and after neoadjuvant treatment did not predict survival.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT01099436 , April 2010.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
Breast cancer research : BCR - 21(2019), 1 vom: 28. Aug., Seite 97 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
de Groot, Stefanie [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.02.2020 Date Revised 09.03.2020 published: Electronic ClinicalTrials.gov: NCT01099436 Citation Status MEDLINE |
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| doi: |
10.1186/s13058-019-1180-6 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM300649851 |
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| 041 | |a eng | ||
| 100 | 1 | |a de Groot, Stefanie |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Addition of zoledronic acid to neoadjuvant chemotherapy is not beneficial in patients with HER2-negative stage II/III breast cancer |b 5-year survival analysis of the NEOZOTAC trial (BOOG 2010-01) |
| 264 | 1 | |c 2019 | |
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| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 26.02.2020 | ||
| 500 | |a Date Revised 09.03.2020 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT01099436 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Adjuvant bisphosphonates are associated with improved breast cancer survival in postmenopausal patients. Addition of zoledronic acid (ZA) to neoadjuvant chemotherapy did not improve pathological complete response in the phase III NEOZOTAC trial. Here we report the results of the secondary endpoints, disease-free survival, (DFS) and overall survival (OS) | ||
| 520 | |a PATIENTS AND METHODS: Patients with HER2-negative, stage II/III breast cancer were randomized to receive the standard 6 cycles of neoadjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy with or without 4 mg intravenous (IV) ZA administered within 24 h of chemotherapy. This was repeated every 21 days for 6 cycles. Cox regression models were used to evaluate the effect of ZA and covariates on DFS and OS. Regression models were used to examine the association between insulin, glucose, insulin growth factor-1 (IGF-1) levels, and IGF-1 receptor (IGF-1R) expression with survival outcomes | ||
| 520 | |a RESULTS: Two hundred forty-six women were eligible for inclusion. After a median follow-up of 6.4 years, OS for all patients was significantly worse for those who received ZA (HR 0.468, 95% CI 0.226-0.967, P = 0.040). DFS was not significantly different between the treatment arms (HR 0.656, 95% CI 0.371-1.160, P = 0.147). In a subgroup analysis of postmenopausal women, no significant difference in DFS or OS was found for those who received ZA compared with the control group (HR 0.464, 95% CI 0.176-1.222, P = 0.120; HR 0.539, 95% CI 0.228-1.273, P = 0.159, respectively). The subgroup analysis of premenopausal patients was not significantly different for DFS and OS ((HR 0.798, 95% CI 0.369-1.725, P = 0.565; HR 0.456, 95% CI 0.156-1.336, P = 0.152, respectively). Baseline IGF-1R expression was not significantly associated with DFS or OS. In a predefined additional study, lower serum levels of insulin were associated with improved DFS (HR 1.025, 95% CI 1.005-1.045, P = 0.014) | ||
| 520 | |a CONCLUSIONS: Our results suggest that ZA in combination with neoadjuvant chemotherapy was associated with a worse OS in breast cancer (both pre- and postmenopausal patients). However, in a subgroup analysis of postmenopausal patients, ZA treatment was not associated with DFS or OS. Also, DFS was not significantly different between both groups. IGF-1R expression in tumor tissue before and after neoadjuvant treatment did not predict survival | ||
| 520 | |a TRIAL REGISTRATION: ClinicalTrials.gov, NCT01099436 , April 2010 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Breast cancer | |
| 650 | 4 | |a IGF-1R | |
| 650 | 4 | |a Insulin | |
| 650 | 4 | |a Neoadjuvant chemotherapy | |
| 650 | 4 | |a Survival | |
| 650 | 4 | |a Zoledronic acid | |
| 650 | 7 | |a Bone Density Conservation Agents |2 NLM | |
| 650 | 7 | |a IGF1 protein, human |2 NLM | |
| 650 | 7 | |a IGF1R protein, human |2 NLM | |
| 650 | 7 | |a Insulin |2 NLM | |
| 650 | 7 | |a Insulin-Like Growth Factor I |2 NLM | |
| 650 | 7 | |a 67763-96-6 |2 NLM | |
| 650 | 7 | |a Zoledronic Acid |2 NLM | |
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| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 700 | 1 | |a Pijl, Hanno |e verfasserin |4 aut | |
| 700 | 1 | |a Charehbili, Ayoub |e verfasserin |4 aut | |
| 700 | 1 | |a van de Ven, Saskia |e verfasserin |4 aut | |
| 700 | 1 | |a Smit, Vincent T H B M |e verfasserin |4 aut | |
| 700 | 1 | |a Meershoek-Klein Kranenbarg, Elma |e verfasserin |4 aut | |
| 700 | 1 | |a Heijns, Joan B |e verfasserin |4 aut | |
| 700 | 1 | |a van Warmerdam, Laurence J C |e verfasserin |4 aut | |
| 700 | 1 | |a Kessels, Lonneke W |e verfasserin |4 aut | |
| 700 | 1 | |a Dercksen, M Wouter |e verfasserin |4 aut | |
| 700 | 1 | |a Pepels, Manon J A E |e verfasserin |4 aut | |
| 700 | 1 | |a van Laarhoven, Hanneke W M |e verfasserin |4 aut | |
| 700 | 1 | |a Vriens, Birgit E P J |e verfasserin |4 aut | |
| 700 | 1 | |a Putter, Hein |e verfasserin |4 aut | |
| 700 | 1 | |a Fiocco, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Liefers, Gerrit-Jan |e verfasserin |4 aut | |
| 700 | 1 | |a van der Hoeven, Jacobus J M |e verfasserin |4 aut | |
| 700 | 1 | |a Nortier, Johan W R |e verfasserin |4 aut | |
| 700 | 1 | |a Kroep, Judith R |e verfasserin |4 aut | |
| 700 | 0 | |a Dutch Breast Cancer Research Group |e verfasserin |4 aut | |
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