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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 2/2019

01-01-2019 | Clinical trial

Efficacy of neoadjuvant pertuzumab in addition to chemotherapy and trastuzumab in routine clinical treatment of patients with primary breast cancer: a multicentric analysis

Authors: Peter A. Fasching, Andreas D. Hartkopf, Paul Gass, Lothar Häberle, Leyla Akpolat-Basci, Alexander Hein, Bernhard Volz, Florin-Andrei Taran, Naiba Nabieva, Birgit Pott, Friedrich Overkamp, Hanna Einarson, Peyman Hadji, Hans Tesch, Johannes Ettl, Diana Lüftner, Markus Wallwiener, Volkmar Müller, Wolfgang Janni, Tanja N. Fehm, Andreas Schneeweiss, Michael Untch, Dirk Pott, Michael P. Lux, Thomas Geyer, Cornelia Liedtke, Harald Seeger, Sarah Wetzig, Arndt Hartmann, Rüdiger Schulz-Wendtland, Erik Belleville, Diethelm Wallwiener, Matthias W. Beckmann, Sara Y. Brucker, Hans-Christian Kolberg

Published in: Breast Cancer Research and Treatment | Issue 2/2019

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Abstract

Purpose

Neoadjuvant combination treatment with chemotherapy (CTX), trastuzumab (TZM), and pertuzumab (PTZ) has been shown to result in higher pathological complete response rates (pCR) in comparison with treatment with chemotherapy and trastuzumab (CTX/TZM). This analysis was aimed at real-world validation of these results from prospective randomized trials.

Methods

In a retrospective analysis conducted in the PRAEGNANT network, patients were eligible for inclusion if they had either received neoadjuvant therapy with CTX/TZM or chemotherapy, trastuzumab, and pertuzumab (CTX/TZM/PTZ) and subsequently underwent surgery for their primary breast cancer. The effect of the two neoadjuvant regimens on pCR in addition to commonly applicable predictors of pCR was analyzed in 300 patients from three study sites, using logistic regression analyses with treatment arm, age, clinical tumor stage, grading, and hormone receptor status as predictors.

Results

pCR with complete disappearance of all tumor cells was seen in 30.2% (n = 58) of patients treated with CTX/TZM and in 52.8% (n = 57) of those treated with CTX/TZM/PTZ. CTX/TZM/PTZ was positively associated with pCR (adjusted odds ratio 2.44; 95% CI 1.49–4.02). Mastectomy rates were not influenced by the therapy.

Conclusions

The results of clinical trials were confirmed in this dataset of patients who were treated outside of clinical trials in everyday routine work. pCR rates can be improved by 20% with pertuzumab in routine clinical use.
Appendix
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Literature
1.
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182CrossRefPubMed
2.
Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792CrossRefPubMed
3.
Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672CrossRefPubMed
4.
Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353:1673–1684CrossRefPubMed
5.
Gianni L, Dafni U, Gelber RD, Azambuja E, Muehlbauer S, Goldhirsch A, Untch M, Smith I, Baselga J, Jackisch C, Cameron D, Mano M et al (2011) Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol 12:236–244CrossRefPubMed
6.
Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V et al (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1273–1283CrossRefPubMedPubMedCentral
7.
Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, Winer EP, Colon-Otero G et al (2014) Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol 32:3744–3752CrossRefPubMedPubMedCentral
8.
Lux MP, Janni W, Hartkopf AD, Nabieva N, Taran FA, Overkamp F, Kolberg HC, Hadji P, Tesch H, Ettl J, Huober J, Lüftner D et al (2017) Update breast cancer 2017—implementation of novel therapies. Geburtshilfe Frauenheilkd 77:1281–1290CrossRefPubMedPubMedCentral
9.
Untch M, Huober J, Jackisch C, Schneeweiss A, Brucker SY, Dall P, Denkert C, Fasching PA, Fehm T, Gerber B, Janni W, Kuhn T et al (2017) Initial Treatment of Patients with Primary Breast Cancer: Evidence, Controversies, Consensus: Spectrum of Opinion of German Specialists at the 15th International St. Gallen Breast Cancer Conference (Vienna 2017). Geburtshilfe und Frauenheilkunde 77:633–644CrossRefPubMedPubMedCentral
10.
von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, Blohmer JU, Jackisch C, Paepke S, Gerber B, Zahm DM, Kummel S et al (2014) Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol 15:747–756CrossRef
11.
Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T et al (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384:164–172CrossRefPubMed
12.
von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, Gerber B, Eiermann W, Hilfrich J, Huober J, Jackisch C, Kaufmann M et al (2012) Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 30:1796–1804CrossRef
13.
Untch M, Loibl S, Bischoff J, Eidtmann H, Kaufmann M, Blohmer JU, Hilfrich J, Strumberg D, Fasching PA, Kreienberg R, Tesch H, Hanusch C et al (2012) Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol 13:135–144CrossRefPubMed
14.
Untch M, Fasching PA, Konecny GE, Hasmuller S, Lebeau A, Kreienberg R, Camara O, Muller V, du Bois A, Kuhn T, Stickeler E, Harbeck N et al (2011) Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol 29:3351–3357CrossRefPubMed
15.
Untch M, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, Bauerfeind I, Hilfrich J, Eidtmann H, Gerber B, Hanusch C, Kuhn T et al (2010) Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol 28:2024–2031CrossRefPubMed
16.
Coudert BP, Largillier R, Arnould L, Chollet P, Campone M, Coeffic D, Priou F, Gligorov J, Martin X, Trillet-Lenoir V, Weber B, Bleuse JP et al (2007) Multicenter phase II trial of neoadjuvant therapy with trastuzumab, docetaxel, and carboplatin for human epidermal growth factor receptor-2-overexpressing stage II or III breast cancer: results of the GETN(A)-1 trial. J Clin Oncol 25:2678–2684CrossRefPubMed
17.
Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, Zambetti M, Vazquez F, Byakhow M, Lichinitser M, Climent MA, Ciruelos E et al (2010) Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet 375:377–384CrossRefPubMed
18.
Fasching PA, Heusinger K, Haeberle L, Niklos M, Hein A, Bayer CM, Rauh C, Schulz-Wendtland R, Bani MR, Schrauder M, Kahmann L, Lux MP et al (2011) Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer 11:486CrossRefPubMedPubMedCentral
19.
Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P et al (2016) 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol 17:791–800CrossRefPubMed
20.
Slamon DJ, Eiermann W, Robert NJ, Giermek J, Martin M, Jasiowka M, Mackey JR, Chan A, Liu MC, Pinter T, Valero V, Falkson C et al (2016) Ten year follow-up of BCIRG-006 comparing doxorubicin plus cyclophosphamide followed by docetaxel (AC -> T) with doxorubicin plus cyclophosphamide followed by docetaxel and trastuzumab (AC -> TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2+ early breast cancer. Cancer Res 5:76
21.
Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, Castro G Jr, Untch M, Smith I, Gianni L, Baselga J, Al-Sakaff N et al (2017) 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet 389:1195–1205CrossRefPubMedPubMedCentral
22.
Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, Roman L, Pedrini JL, Pienkowski T, Knott A, Clark E, Benyunes MC et al (2012) Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366:109–119CrossRefPubMed
23.
Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B et al (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13:25–32CrossRefPubMed
24.
Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G et al (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 24:2278–2284CrossRefPubMed
25.
Swain SM, Ewer MS, Viale G, Delaloge S, Ferrero JM, Verrill M, Colomer R, Vieira C, Werner TL, Douthwaite H, Bradley D, Waldron-Lynch M et al (2017) Primary analysis of BERENICE: a phase II cardiac safety study of pertuzumab, trastuzumab, and neoadjuvant anthracycline-based chemotherapy in patients with locally advanced, inflammatory, or early-stage, unilateral, and invasive HER2-positive breast cancer. Cancer Res 77:P4–P21
26.
27.
28.
29.
von Minckwitz G, Procter M, de Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A, Lang I et al (2017) Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med 377:122–131CrossRef
30.
Fasching PA, Brucker SY, Fehm TN, Overkamp F, Janni W, Wallwiener M, Hadji P, Belleville E, Haberle L, Taran FA, Luftner D, Lux MP et al (2015) Biomarkers in patients with metastatic breast cancer and the praegnant study network. Geburtshilfe Frauenheilkd 75:41–50CrossRefPubMedPubMedCentral
31.
Hein A, Gass P, Walter CB, Taran FA, Hartkopf A, Overkamp F, Kolberg HC, Hadji P, Tesch H, Ettl J, Wuerstlein R, Lounsbury D et al (2016) Computerized patient identification for the EMBRACA clinical trial using real-time data from the PRAEGNANT network for metastatic breast cancer patients. Breast Cancer Res Treat 158:59–65CrossRefPubMed
32.
Fremd C, Hack CC, Schneeweiss A, Rauch G, Wallwiener D, Brucker SY, Taran FA, Hartkopf A, Overkamp F, Tesch H, Fehm T, Hadji P et al (2017) Use of complementary and integrative medicine among German breast cancer patients: predictors and implications for patient care within the PRAEGNANT study network. Arch Gynecol Obstet 295:1239–1245CrossRefPubMed
33.
Salmen J, Neugebauer J, Fasching PA, Haeberle L, Huober J, Wockel A, Rauh C, Schuetz F, Weissenbacher T, Kost B, Stickeler E, Klar M et al (2014) Pooled analysis of the prognostic relevance of progesterone receptor status in five German cohort studies. Breast Cancer Res Treat 148:143–151CrossRefPubMed
34.
Haberle L, Fasching PA, Brehm B, Heusinger K, Jud SM, Loehberg CR, Hack CC, Preuss C, Lux MP, Hartmann A, Vachon CM, Meier-Meitinger M et al (2016) Mammographic density is the main correlate of tumors detected on ultrasound but not on mammography. Int J Cancer 139:1967–1974CrossRefPubMed
35.
Burghaus S, Haberle L, Schrauder MG, Heusinger K, Thiel FC, Hein A, Wachter D, Strehl J, Hartmann A, Ekici AB, Renner SP, Beckmann MW et al (2015) Endometriosis as a risk factor for ovarian or endometrial cancer—results of a hospital-based case-control study. BMC cancer 15:751CrossRefPubMedPubMedCentral
36.
Beitsch P, Whitworth P, Baron P, Rotkis MC, Mislowsky AM, Richards PD, Murray MK, Pellicane JV, Dul CL, Nash CH, Stork-Sloots L, de Snoo F et al (2017) Pertuzumab/trastuzumab/CT versus trastuzumab/CT therapy for HER2+ breast cancer: results from the prospective Neoadjuvant Breast Registry Symphony Trial (NBRST). Ann Surg Oncol 24:2539–2546CrossRefPubMed
37.
Swain SM, Schneeweiss A, Gianni L, Gao JJ, Stein A, Waldron-Lynch M, Heeson S, Beattie MS, Yoo B, Cortes J, Baselga J (2017) Incidence and management of diarrhea in patients with HER2-positive breast cancer treated with pertuzumab. Ann Oncol 28:761–768PubMedPubMedCentral
38.
Squires H, Pandor A, Thokala P, Stevens JW, Kaltenthaler E, Clowes M, Coleman R, Wyld L (2017) Pertuzumab for the neoadjuvant treatment of early-stage HER2-positive breast cancer: an evidence review group perspective of a NICE single technology appraisal. Pharmacoeconomics 7:10
39.
Hennigs A, Riedel F, Marme F, Sinn P, Lindel K, Gondos A, Smetanay K, Golatta M, Sohn C, Schuetz F, Heil J, Schneeweiss A (2016) Changes in chemotherapy usage and outcome of early breast cancer patients in the last decade. Breast Cancer Res Treat 160:491–499CrossRefPubMedPubMedCentral
Metadata
Title
Efficacy of neoadjuvant pertuzumab in addition to chemotherapy and trastuzumab in routine clinical treatment of patients with primary breast cancer: a multicentric analysis
Authors
Peter A. Fasching
Andreas D. Hartkopf
Paul Gass
Lothar Häberle
Leyla Akpolat-Basci
Alexander Hein
Bernhard Volz
Florin-Andrei Taran
Naiba Nabieva
Birgit Pott
Friedrich Overkamp
Hanna Einarson
Peyman Hadji
Hans Tesch
Johannes Ettl
Diana Lüftner
Markus Wallwiener
Volkmar Müller
Wolfgang Janni
Tanja N. Fehm
Andreas Schneeweiss
Michael Untch
Dirk Pott
Michael P. Lux
Thomas Geyer
Cornelia Liedtke
Harald Seeger
Sarah Wetzig
Arndt Hartmann
Rüdiger Schulz-Wendtland
Erik Belleville
Diethelm Wallwiener
Matthias W. Beckmann
Sara Y. Brucker
Hans-Christian Kolberg
Publication date
01-01-2019
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-018-5008-3

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