Trial of Neoadjuvant THP vs TCHP for HER2-Amplified/Positive Breast Cancer

Summary

This is a randomized phase II study to evaluate the pathological complete response (pCR) rate with two neoadjuvant regimens (Docetaxel+Carboplatin+Herceptin/Perjeta and Docetaxel+Herceptin/Perjeta) in HER2 amplified/positive early breast cancer.

Timeline

Start

2025-11-14

Primary completion

2027-11-14

Completion

2031-05-14

Publications

• Background Harris, J., M. Morrow, and L. Norton, Malignant tumors of the breast, in Cancer: principles and practice of oncology, V.J. DeVita, S. Hellman, and S. Rosenberg, Editors. 1997, Lippincott-Raven: Philadelphia. p. 1557-1602.
• Background Untch M, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, Bauerfeind I, Hilfrich J, Eidtmann H, Gerber B, Hanusch C, Kuhn T, du Bois A, Blohmer JU, Thomssen C, Dan Costa S, Jackisch C, Kaufmann M, Mehta K, von Minckwitz G. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010 Apr 20;28(12):2024-31. doi: 10.1200/JCO.2009.23.8451. Epub 2010 Mar 22.
• Background Broglio KR, Quintana M, Foster M, Olinger M, McGlothlin A, Berry SM, Boileau JF, Brezden-Masley C, Chia S, Dent S, Gelmon K, Paterson A, Rayson D, Berry DA. Association of Pathologic Complete Response to Neoadjuvant Therapy in HER2-Positive Breast Cancer With Long-Term Outcomes: A Meta-Analysis. JAMA Oncol. 2016 Jun 1;2(6):751-60. doi: 10.1001/jamaoncol.2015.6113.
• Background Bear HD. Indications for neoadjuvant chemotherapy for breast cancer. Semin Oncol. 1998 Apr;25(2 Suppl 3):3-12. No abstract available.
• Background Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, Wickerham DL, Begovic M, DeCillis A, Robidoux A, Margolese RG, Cruz AB Jr, Hoehn JL, Lees AW, Dimitrov NV, Bear HD. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998 Aug;16(8):2672-85. doi: 10.1200/JCO.1998.16.8.2672.
• Background Kuerer HM, Newman LA, Smith TL, Ames FC, Hunt KK, Dhingra K, Theriault RL, Singh G, Binkley SM, Sneige N, Buchholz TA, Ross MI, McNeese MD, Buzdar AU, Hortobagyi GN, Singletary SE. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999 Feb;17(2):460-9. doi: 10.1200/JCO.1999.17.2.460.
• Background Green M, Hortobagyi GN. Neoadjuvant chemotherapy for operable breast cancer. Oncology (Williston Park). 2002 Jul;16(7):871-84, 889; discussion 889-90, 892-4, 897-8.
• Background van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001 Nov 15;19(22):4224-37. doi: 10.1200/JCO.2001.19.22.4224.
• Background Valero V, Buzdar AU, McNeese M, Singletary E, Hortobagyi GN. Primary chemotherapy in the treatment of breast cancer: the University of Texas M. D. Anderson Cancer Center experience. Clin Breast Cancer. 2002 Oct;3 Suppl 2:S63-8. doi: 10.3816/cbc.2002.s.014.
• Background Wang J, Buchholz TA, Middleton LP, Allred DC, Tucker SL, Kuerer HM, Esteva FJ, Hortobagyi GN, Sahin AA. Assessment of histologic features and expression of biomarkers in predicting pathologic response to anthracycline-based neoadjuvant chemotherapy in patients with breast carcinoma. Cancer. 2002 Jun 15;94(12):3107-14. doi: 10.1002/cncr.10585.
• Background Cortazar, P., et al., Meta-analysis results from the collaborative trials in neoadjuvant breast cancer (CTNeoBC) [abstract]. Cancer Res, 2012. 72(24 Suppl): p. Abstract nr P1-14-20.
• Background Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J; Breast Cancer International Research Group. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83. doi: 10.1056/NEJMoa0910383.
• Background Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortes J. 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. 2013 Sep;24(9):2278-84. doi: 10.1093/annonc/mdt182. Epub 2013 May 22.
• Background 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, Eidtmann H, Klare P, Huober J, Costa S, Tesch H, Hanusch C, Hilfrich J, Khandan F, Fasching PA, Sinn BV, Engels K, Mehta K, Nekljudova V, Untch M. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014 Jun;15(7):747-56. doi: 10.1016/S1470-2045(14)70160-3. Epub 2014 Apr 30.
• Background Villacampa G, Matikas A, Oliveira M, Prat A, Pascual T, Papakonstantinou A. Landscape of neoadjuvant therapy in HER2-positive breast cancer: a systematic review and network meta-analysis. Eur J Cancer. 2023 Sep;190:112885. doi: 10.1016/j.ejca.2023.03.042. Epub 2023 Apr 8.
• Background Lin B, Fan J, Liu F, Wen Y, Li J, Gao F, Zhang Y, Feng G, Du X, Chen W. Efficacy and Safety of Dual Anti-HER2 Blockade and Docetaxel With or Without Carboplatin as Neoadjuvant Regimen for Treatment of HER2-Positive Breast Cancer. Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231218152. doi: 10.1177/15330338231218152.
• Background Lv M, Guo H, Wang C, Tian P, Ma Y, Chen X, Luo S. Neoadjuvant docetaxel with or without carboplatin plus dual HER2 blockade for HER2-positive breast cancer: a retrospective multi-center Chinese study. Gland Surg. 2020 Dec;9(6):2079-2090. doi: 10.21037/gs-20-791.
• Background Waks AG, Desai NV, Li T, Poorvu PD, Partridge AH, Sinclair N, Spring LM, Faggen M, Constantine M, Metzger O, Alberti J, Deane J, Rosenberg SM, Frank E, Tolaney SM, Krop IE, Tung NM, Tayob N, King TA, Mittendorf EA, Winer EP. A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer. NPJ Breast Cancer. 2022 May 10;8(1):63. doi: 10.1038/s41523-022-00429-7.
• Background Chen XC, Jiao DC, Qiao JH, Wang CZ, Sun XF, Lu ZD, Li LF, Zhang CJ, Yan M, Wei Y, Chen B, Feng YQ, Deng M, Ma MD, Plichta JK, He YW, Liu ZZ. De-escalated neoadjuvant weekly nab-paclitaxel with trastuzumab and pertuzumab versus docetaxel, carboplatin, trastuzumab, and pertuzumab in patients with HER2-positive early breast cancer (HELEN-006): a multicentre, randomised, phase 3 trial. Lancet Oncol. 2025 Jan;26(1):27-36. doi: 10.1016/S1470-2045(24)00581-3. Epub 2024 Nov 26.
• Background 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, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P. 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. 2012 Jan;13(1):25-32. doi: 10.1016/S1470-2045(11)70336-9. Epub 2011 Dec 6.
• Background Ismael G, Hegg R, Muehlbauer S, Heinzmann D, Lum B, Kim SB, Pienkowski T, Lichinitser M, Semiglazov V, Melichar B, Jackisch C. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol. 2012 Sep;13(9):869-78. doi: 10.1016/S1470-2045(12)70329-7. Epub 2012 Aug 9.
• Background Tan AR, Im SA, Mattar A, Colomer R, Stroyakovskii D, Nowecki Z, De Laurentiis M, Pierga JY, Jung KH, Schem C, Hogea A, Badovinac Crnjevic T, Heeson S, Shivhare M, Kirschbrown WP, Restuccia E, Jackisch C; FeDeriCa study group. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2021 Jan;22(1):85-97. doi: 10.1016/S1470-2045(20)30536-2. Epub 2020 Dec 21.
• Background Bueno-Muino C, Echavarria I, Lopez-Tarruella S, Roche-Molina M, Del Monte-Millan M, Massarrah T, Jerez Y, Ayala de la Pena F, Garcia-Saenz JA, Moreno F, Rodriguez-Lescure A, Malon-Gimenez D, Ballesteros Garcia AI, Marin-Aguilera M, Galvan P, Braso-Maristany F, Waks AG, Tolaney SM, Mittendorf EA, Vivancos A, Villagrasa P, Parker JS, Perou CM, Pare L, Villacampa G, Prat A, Martin M. Assessment of a Genomic Assay in Patients With ERBB2-Positive Breast Cancer Following Neoadjuvant Trastuzumab-Based Chemotherapy With or Without Pertuzumab. JAMA Oncol. 2023 Jun 1;9(6):841-846. doi: 10.1001/jamaoncol.2023.0187.
• Background Villacampa G, Tung NM, Pernas S, Pare L, Bueno-Muino C, Echavarria I, Lopez-Tarruella S, Roche-Molina M, Del Monte-Millan M, Marin-Aguilera M, Braso-Maristany F, Waks AG, Pascual T, Martinez-Saez O, Vivancos A, Conte PF, Guarneri V, Vittoria Dieci M, Griguolo G, Cortes J, Llombart-Cussac A, Munoz M, Vidal M, Adamo B, Wolff AC, DeMichele A, Villagrasa P, Parker JS, Perou CM, Fernandez-Martinez A, Carey LA, Mittendorf EA, Martin M, Prat A, Tolaney SM. Association of HER2DX with pathological complete response and survival outcomes in HER2-positive breast cancer. Ann Oncol. 2023 Sep;34(9):783-795. doi: 10.1016/j.annonc.2023.05.012. Epub 2023 Jun 9.
• Background Llombart-Cussac A, Perez-Garcia J, Braso-Maristany F, Pare L, Villacampa G, Gion M, Schmid P, Colleoni M, Borrego MR, Galvan P, Parker JS, Buckingham W, Perou CM, Villagrasa P, Guerrero JA, Sampayo-Cordero M, Mancino M, Prat A, Cortes J. HER2DX Genomic Assay in HER2-Positive Early Breast Cancer Treated with Trastuzumab and Pertuzumab: A Correlative Analysis from the PHERGain Phase II Trial. Clin Cancer Res. 2024 Sep 13;30(18):4123-4130. doi: 10.1158/1078-0432.CCR-24-0464.
• Background Waks AG, Ogayo ER, Pare L, Marin-Aguilera M, Braso-Maristany F, Galvan P, Castillo O, Martinez-Saez O, Vivancos A, Villagrasa P, Villacampa G, Tarantino P, Desai N, Guerriero J, Metzger O, Tung NM, Krop IE, Parker JS, Perou CM, Prat A, Winer EP, Tolaney SM, Mittendorf EA. Assessment of the HER2DX Assay in Patients With ERBB2-Positive Breast Cancer Treated With Neoadjuvant Paclitaxel, Trastuzumab, and Pertuzumab. JAMA Oncol. 2023 Jun 1;9(6):835-840. doi: 10.1001/jamaoncol.2023.0181.
• Background Yau C, Osdoit M, van der Noordaa M, Shad S, Wei J, de Croze D, Hamy AS, Lae M, Reyal F, Sonke GS, Steenbruggen TG, van Seijen M, Wesseling J, Martin M, Del Monte-Millan M, Lopez-Tarruella S; I-SPY 2 Trial Consortium; Boughey JC, Goetz MP, Hoskin T, Gould R, Valero V, Edge SB, Abraham JE, Bartlett JMS, Caldas C, Dunn J, Earl H, Hayward L, Hiller L, Provenzano E, Sammut SJ, Thomas JS, Cameron D, Graham A, Hall P, Mackintosh L, Fan F, Godwin AK, Schwensen K, Sharma P, DeMichele AM, Cole K, Pusztai L, Kim MO, van 't Veer LJ, Esserman LJ, Symmans WF. Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients. Lancet Oncol. 2022 Jan;23(1):149-160. doi: 10.1016/S1470-2045(21)00589-1. Epub 2021 Dec 11.
• Background Hudis CA, Barlow WE, Costantino JP, Gray RJ, Pritchard KI, Chapman JA, Sparano JA, Hunsberger S, Enos RA, Gelber RD, Zujewski JA. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007 May 20;25(15):2127-32. doi: 10.1200/JCO.2006.10.3523.
• Background Wolff AC, Somerfield MR, Dowsett M, Hammond MEH, Hayes DF, McShane LM, Saphner TJ, Spears PA, Allison KH. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. Arch Pathol Lab Med. 2023 Sep 1;147(9):993-1000. doi: 10.5858/arpa.2023-0950-SA.

Drugs

Indications