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Erschienen in: Breast Cancer Research and Treatment 3/2020

01.02.2020 | Review

Adjuvant addition of capecitabine to early-stage triple-negative breast cancer patients receiving standard chemotherapy: a meta-analysis

verfasst von: Yan Li, Yidong Zhou, Feng Mao, Yan Lin, Xiaohui Zhang, Songjie Shen, Qiang Sun

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2020

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Abstract

Purpose

Triple-negative breast cancer (TNBC) pertains to a breast cancer subtype that has the highest metastatic and recurrence rates. The effectiveness of capecitabine as adjuvant chemotherapy for TNBC has remained unclear. This study conducted a meta-analysis of the efficacy of capecitabine as adjuvant chemotherapy for early-stage TNBC treated with taxane-/anthracycline-based chemotherapy.

Methods

We identified relevant research reports in online databases until May 2019. We finally included seven randomized clinical trials to perform this meta-analysis. Altogether, the seven trials enrolled 3151 early-stage TNBC patients, with 1552 receiving standard (neo)adjuvant chemotherapy regimens and 1599 receiving addition of capecitabine in the adjuvant settings besides standard regimens.

Results

A meta-analysis of the seven trials revealed a significant increase in disease-free survival (DFS) with the addition of capecitabine (Hazard ratio (HR) = 0.77, 95% CI 0.66–0.90). This improvement in DFS was significant both in trials conducted in America-Europe and in Asia. In trials involving six to eight cycles of capecitabine addition, we observed a significant improvement in DFS. Furthermore, in the meta-analysis of six trials, we detected a significant increase in overall survival (OS) favoring capecitabine (HR = 0.69, 95% CI 0.56–0.85).

Conclusions

Adjuvant addition of capecitabine to early-stage TNBC patients receiving standard chemotherapy showed significant DFS and OS improvement. Future studies involving the selection of patients that may have the highest survival benefit from adding capecitabine are warranted.
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Literatur
2.
Zurück zum Zitat Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P, Taylor C, Wang YC, Bergh J, Di Leo A, Albain K, Swain S, Piccart M, Pritchard K (2012) Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379(9814):432–444. https://doi.org/10.1016/s0140-6736(11)61625-5 CrossRefPubMed Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, Cutter D, Darby S, McGale P, Taylor C, Wang YC, Bergh J, Di Leo A, Albain K, Swain S, Piccart M, Pritchard K (2012) Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 379(9814):432–444. https://​doi.​org/​10.​1016/​s0140-6736(11)61625-5 CrossRefPubMed
4.
Zurück zum Zitat Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Kim YH, Ji J, Yeh TS, Button P, Sirzen F, Noh SH, for the CLASSIC trial investigators (2012) Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 379(9813):315–321. https://doi.org/10.1016/S0140-6736(11)61873-4 CrossRefPubMed Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Kim YH, Ji J, Yeh TS, Button P, Sirzen F, Noh SH, for the CLASSIC trial investigators (2012) Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 379(9813):315–321. https://​doi.​org/​10.​1016/​S0140-6736(11)61873-4 CrossRefPubMed
5.
Zurück zum Zitat Noh SH, Park SR, Yang HK, Chung HC, Chung IJ, Kim SW, Kim HH, Choi JH, Kim HK, Yu W, Lee JI, Shin DB, Ji J, Chen JS, Lim Y, Ha S, Bang YJ, investigators Ct (2014) Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol 15(12):1389–1396. https://doi.org/10.1016/S1470-2045(14)70473-5 CrossRefPubMed Noh SH, Park SR, Yang HK, Chung HC, Chung IJ, Kim SW, Kim HH, Choi JH, Kim HK, Yu W, Lee JI, Shin DB, Ji J, Chen JS, Lim Y, Ha S, Bang YJ, investigators Ct (2014) Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol 15(12):1389–1396. https://​doi.​org/​10.​1016/​S1470-2045(14)70473-5 CrossRefPubMed
6.
Zurück zum Zitat Pallis AG, Boukovinas I, Ardavanis A, Varthalitis I, Malamos N, Georgoulias V, Mavroudis D (2012) A multicenter randomized phase III trial of vinorelbine/gemcitabine doublet versus capecitabine monotherapy in anthracycline- and taxane-pretreated women with metastatic breast cancer. Ann Oncol 23(5):1164–1169. https://doi.org/10.1093/annonc/mdr405 CrossRefPubMed Pallis AG, Boukovinas I, Ardavanis A, Varthalitis I, Malamos N, Georgoulias V, Mavroudis D (2012) A multicenter randomized phase III trial of vinorelbine/gemcitabine doublet versus capecitabine monotherapy in anthracycline- and taxane-pretreated women with metastatic breast cancer. Ann Oncol 23(5):1164–1169. https://​doi.​org/​10.​1093/​annonc/​mdr405 CrossRefPubMed
7.
Zurück zum Zitat Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355(26):2733–2743. https://doi.org/10.1056/NEJMoa064320 CrossRefPubMed Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355(26):2733–2743. https://​doi.​org/​10.​1056/​NEJMoa064320 CrossRefPubMed
8.
Zurück zum Zitat Miles D, von Minckwitz G, Seidman AD (2002) Combination versus sequential single-agent therapy in metastatic breast cancer. Oncologist 7(Suppl 6):13–19PubMed Miles D, von Minckwitz G, Seidman AD (2002) Combination versus sequential single-agent therapy in metastatic breast cancer. Oncologist 7(Suppl 6):13–19PubMed
10.
Zurück zum Zitat Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Kokko R, Ahlgren J, Auvinen P, Lahdenpera O, Kosonen S, Villman K, Nyandoto P, Nilsson G, Poikonen-Saksela P, Kataja V, Junnila J, Bono P, Lindman H (2017) Adjuvant capecitabine in combination with docetaxel, epirubicin, and cyclophosphamide for early breast cancer: the randomized clinical FinXX trial. JAMA Oncol 3(6):793–800. https://doi.org/10.1001/jamaoncol.2016.6120 CrossRefPubMedPubMedCentral Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Kokko R, Ahlgren J, Auvinen P, Lahdenpera O, Kosonen S, Villman K, Nyandoto P, Nilsson G, Poikonen-Saksela P, Kataja V, Junnila J, Bono P, Lindman H (2017) Adjuvant capecitabine in combination with docetaxel, epirubicin, and cyclophosphamide for early breast cancer: the randomized clinical FinXX trial. JAMA Oncol 3(6):793–800. https://​doi.​org/​10.​1001/​jamaoncol.​2016.​6120 CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Kokko R, Ahlgren J, Auvinen P, Paija O, Helle L, Villman K, Nyandoto P, Nilsson G, Pajunen M, Asola R, Poikonen P, Leinonen M, Kataja V, Bono P, Lindman H (2012) Adjuvant capecitabine, docetaxel, cyclophosphamide, and epirubicin for early breast cancer: final analysis of the randomized FinXX trial. J Clin Oncol 30(1):11–18. https://doi.org/10.1200/jco.2011.35.4639 CrossRefPubMed Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Kokko R, Ahlgren J, Auvinen P, Paija O, Helle L, Villman K, Nyandoto P, Nilsson G, Pajunen M, Asola R, Poikonen P, Leinonen M, Kataja V, Bono P, Lindman H (2012) Adjuvant capecitabine, docetaxel, cyclophosphamide, and epirubicin for early breast cancer: final analysis of the randomized FinXX trial. J Clin Oncol 30(1):11–18. https://​doi.​org/​10.​1200/​jco.​2011.​35.​4639 CrossRefPubMed
12.
Zurück zum Zitat Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Kokko R, Ahlgren J, Auvinen P, Saarni O, Helle L, Villman K, Nyandoto P, Nilsson G, Leinonen M, Kataja V, Bono P, Lindman H (2014) Outcome of patients with HER2-positive breast cancer treated with or without adjuvant trastuzumab in the Finland capecitabine trial (FinXX). Acta Oncol 53(2):186–194. https://doi.org/10.3109/0284186x.2013.820840 CrossRefPubMed Joensuu H, Kellokumpu-Lehtinen PL, Huovinen R, Jukkola-Vuorinen A, Tanner M, Kokko R, Ahlgren J, Auvinen P, Saarni O, Helle L, Villman K, Nyandoto P, Nilsson G, Leinonen M, Kataja V, Bono P, Lindman H (2014) Outcome of patients with HER2-positive breast cancer treated with or without adjuvant trastuzumab in the Finland capecitabine trial (FinXX). Acta Oncol 53(2):186–194. https://​doi.​org/​10.​3109/​0284186x.​2013.​820840 CrossRefPubMed
13.
Zurück zum Zitat O'Shaughnessy J, Koeppen H, Xiao Y, Lackner MR, Paul D, Stokoe C, Pippen J Jr, Krekow L, Holmes FA, Vukelja S, Lindquist D, Sedlacek S, Rivera R, Brooks R, McIntyre K, Brownstein C, Hoersch S, Blum JL, Jones S (2015) Patients with slowly proliferative early breast cancer have low five-year recurrence rates in a phase III adjuvant trial of capecitabine. Clin Cancer Res 21(19):4305–4311. https://doi.org/10.1158/1078-0432.ccr-15-0636 CrossRefPubMed O'Shaughnessy J, Koeppen H, Xiao Y, Lackner MR, Paul D, Stokoe C, Pippen J Jr, Krekow L, Holmes FA, Vukelja S, Lindquist D, Sedlacek S, Rivera R, Brooks R, McIntyre K, Brownstein C, Hoersch S, Blum JL, Jones S (2015) Patients with slowly proliferative early breast cancer have low five-year recurrence rates in a phase III adjuvant trial of capecitabine. Clin Cancer Res 21(19):4305–4311. https://​doi.​org/​10.​1158/​1078-0432.​ccr-15-0636 CrossRefPubMed
14.
15.
Zurück zum Zitat Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, Kuroi K, Im SA, Park BW, Kim SB, Yanagita Y, Ohno S, Takao S, Aogi K, Iwata H, Jeong J, Kim A, Park KH, Sasano H, Ohashi Y, Toi M (2017) Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med 376(22):2147–2159. https://doi.org/10.1056/NEJMoa1612645 CrossRefPubMed Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, Kuroi K, Im SA, Park BW, Kim SB, Yanagita Y, Ohno S, Takao S, Aogi K, Iwata H, Jeong J, Kim A, Park KH, Sasano H, Ohashi Y, Toi M (2017) Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med 376(22):2147–2159. https://​doi.​org/​10.​1056/​NEJMoa1612645 CrossRefPubMed
21.
Zurück zum Zitat Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17(1):1–12CrossRefPubMed Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17(1):1–12CrossRefPubMed
24.
Zurück zum Zitat Zhimin S, Li J, Pang D, Wang C, Jiang J, Yang S, Liu Y, Fu PF, Sheng Y, Zhang G, Cao L (2016) Cbcsg-10: adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for triple negative breast cancer (2012–2016). 2016 ASCO Annual Meeting|Virtual Meeting|Meeting Library. China Breast Cancer Clinical Study Group. https://meetinglibrary.asco.org/content/123895?media=vm.html. Accessed 26 Apr 2019 Zhimin S, Li J, Pang D, Wang C, Jiang J, Yang S, Liu Y, Fu PF, Sheng Y, Zhang G, Cao L (2016) Cbcsg-10: adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for triple negative breast cancer (2012–2016). 2016 ASCO Annual Meeting|Virtual Meeting|Meeting Library. China Breast Cancer Clinical Study Group. https://​meetinglibrary.​asco.​org/​content/​123895?​media=​vm.​html. Accessed 26 Apr 2019
25.
Zurück zum Zitat Martin M, Ruiz Simon A, Ruiz Borrego M, Ribelles N, Rodriguez-Lescure A, Munoz-Mateu M, Gonzalez S, Margeli Vila M, Barnadas A, Ramos M, Del Barco BS, Jara C, Calvo L, Martinez-Janez N, Mendiola Fernandez C, Rodriguez CA, Martinez de Duenas E, Andres R, Plazaola A, de la Haba-Rodriguez J, Lopez-Vega JM, Adrover E, Ballesteros AI, Santaballa A, Sanchez-Rovira P, Baena-Canada JM, Casas M, del Carmen CM, Carrasco EM, Lluch A (2015) Epirubicin plus cyclophosphamide followed by docetaxel versus epirubicin plus docetaxel followed by capecitabine as adjuvant therapy for node-positive early breast cancer: results from the GEICAM/2003-10 Study. J Clin Oncol 33(32):3788–3795. https://doi.org/10.1200/JCO.2015.61.9510 CrossRefPubMed Martin M, Ruiz Simon A, Ruiz Borrego M, Ribelles N, Rodriguez-Lescure A, Munoz-Mateu M, Gonzalez S, Margeli Vila M, Barnadas A, Ramos M, Del Barco BS, Jara C, Calvo L, Martinez-Janez N, Mendiola Fernandez C, Rodriguez CA, Martinez de Duenas E, Andres R, Plazaola A, de la Haba-Rodriguez J, Lopez-Vega JM, Adrover E, Ballesteros AI, Santaballa A, Sanchez-Rovira P, Baena-Canada JM, Casas M, del Carmen CM, Carrasco EM, Lluch A (2015) Epirubicin plus cyclophosphamide followed by docetaxel versus epirubicin plus docetaxel followed by capecitabine as adjuvant therapy for node-positive early breast cancer: results from the GEICAM/2003-10 Study. J Clin Oncol 33(32):3788–3795. https://​doi.​org/​10.​1200/​JCO.​2015.​61.​9510 CrossRefPubMed
26.
Zurück zum Zitat Furlanetto J, Eiermann W, Marme F, Reimer T, Reinisch M, Schmatloch S, Stickeler E, Thomssen C, Untch M, Denkert C, von Minckwitz G, Lederer B, Nekljudova V, Weber K, Loibl S, Mobus V (2016) Higher rate of severe toxicities in obese patients receiving dose-dense (dd) chemotherapy according to unadjusted body surface area: results of the prospectively randomized GAIN Study. Ann Oncol 27(11):2053–2059. https://doi.org/10.1093/annonc/mdw315 CrossRefPubMed Furlanetto J, Eiermann W, Marme F, Reimer T, Reinisch M, Schmatloch S, Stickeler E, Thomssen C, Untch M, Denkert C, von Minckwitz G, Lederer B, Nekljudova V, Weber K, Loibl S, Mobus V (2016) Higher rate of severe toxicities in obese patients receiving dose-dense (dd) chemotherapy according to unadjusted body surface area: results of the prospectively randomized GAIN Study. Ann Oncol 27(11):2053–2059. https://​doi.​org/​10.​1093/​annonc/​mdw315 CrossRefPubMed
27.
Zurück zum Zitat Kelly CM, Green MC, Broglio K, Thomas ES, Brewster AM, Valero V, Ibrahim NK, Gonzalez-Angulo AM, Booser DJ, Walters RS, Hunt KK, Hortobagyi GN, Buzdar AU (2012) Phase III trial evaluating weekly paclitaxel versus docetaxel in combination with capecitabine in operable breast cancer. J Clin Oncol 30(9):930–935. https://doi.org/10.1200/jco.2011.36.2079 CrossRefPubMed Kelly CM, Green MC, Broglio K, Thomas ES, Brewster AM, Valero V, Ibrahim NK, Gonzalez-Angulo AM, Booser DJ, Walters RS, Hunt KK, Hortobagyi GN, Buzdar AU (2012) Phase III trial evaluating weekly paclitaxel versus docetaxel in combination with capecitabine in operable breast cancer. J Clin Oncol 30(9):930–935. https://​doi.​org/​10.​1200/​jco.​2011.​36.​2079 CrossRefPubMed
28.
Zurück zum Zitat Mobus V, von Minckwitz G, Jackisch C, Luck HJ, Schneeweiss A, Tesch H, Elling D, Harbeck N, Conrad B, Fehm T, Huober J, Muller V, Bauerfeind I, du Bois A, Loibl S, Nekljudova V, Untch M, Thomssen C (2017) German Adjuvant Intergroup Node-positive Study (GAIN): a phase III trial comparing two dose-dense regimens (iddEPC versus ddEC-PwX) in high-risk early breast cancer patients. Ann Oncol 28(8):1803–1810. https://doi.org/10.1093/annonc/mdx203 CrossRefPubMed Mobus V, von Minckwitz G, Jackisch C, Luck HJ, Schneeweiss A, Tesch H, Elling D, Harbeck N, Conrad B, Fehm T, Huober J, Muller V, Bauerfeind I, du Bois A, Loibl S, Nekljudova V, Untch M, Thomssen C (2017) German Adjuvant Intergroup Node-positive Study (GAIN): a phase III trial comparing two dose-dense regimens (iddEPC versus ddEC-PwX) in high-risk early breast cancer patients. Ann Oncol 28(8):1803–1810. https://​doi.​org/​10.​1093/​annonc/​mdx203 CrossRefPubMed
29.
Zurück zum Zitat von Minckwitz G, Conrad B, Reimer T, Decker T, Eidtmann H, Eiermann W, Hackmann J, Mobus V, Marme F, Potenberg J, Stickeler E, Simon E, Thomssen C, Huober J, Denkert C, Alfer J, Jackisch C, Nekljudova V, Burchardi N, Loibl S (2015) A randomized phase 2 study comparing EC or CMF versus nab-paclitaxel plus capecitabine as adjuvant chemotherapy for nonfrail elderly patients with moderate to high-risk early breast cancer (ICE II-GBG 52). Cancer 121(20):3639–3648. https://doi.org/10.1002/cncr.29506 CrossRef von Minckwitz G, Conrad B, Reimer T, Decker T, Eidtmann H, Eiermann W, Hackmann J, Mobus V, Marme F, Potenberg J, Stickeler E, Simon E, Thomssen C, Huober J, Denkert C, Alfer J, Jackisch C, Nekljudova V, Burchardi N, Loibl S (2015) A randomized phase 2 study comparing EC or CMF versus nab-paclitaxel plus capecitabine as adjuvant chemotherapy for nonfrail elderly patients with moderate to high-risk early breast cancer (ICE II-GBG 52). Cancer 121(20):3639–3648. https://​doi.​org/​10.​1002/​cncr.​29506 CrossRef
Metadaten
Titel
Adjuvant addition of capecitabine to early-stage triple-negative breast cancer patients receiving standard chemotherapy: a meta-analysis
verfasst von
Yan Li
Yidong Zhou
Feng Mao
Yan Lin
Xiaohui Zhang
Songjie Shen
Qiang Sun
Publikationsdatum
01.02.2020
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 3/2020
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-019-05513-4

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