Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial

F J Esteva, Y V Baranau, V Baryash, A Manikhas, V Moiseyenko, G Dzagnidze, E Zhavrid, D Boliukh, D Stroyakovskiy, J Pikiel, A E Eniu, R K Li, A V Rusyn, B Tiangco, S J Lee, S Young Lee, S Y Yu, J Stebbing, F J Esteva, Y V Baranau, V Baryash, A Manikhas, V Moiseyenko, G Dzagnidze, E Zhavrid, D Boliukh, D Stroyakovskiy, J Pikiel, A E Eniu, R K Li, A V Rusyn, B Tiangco, S J Lee, S Young Lee, S Y Yu, J Stebbing

Abstract

Purpose: Neoadjuvant CT-P6, a trastuzumab biosimilar, demonstrated equivalent efficacy to reference trastuzumab in a phase 3 trial of HER2-positive early-stage breast cancer (EBC) (NCT02162667). We report post hoc analyses evaluating pathological complete response (pCR) and breast pCR alongside additional efficacy and safety measures.

Methods: Following neoadjuvant treatment and surgery, patients received adjuvant CT-P6 or trastuzumab (6 mg/kg) every 3 weeks for ≤ 1 year.

Results: In total, 271 and 278 patients received CT-P6 and trastuzumab, respectively. pCR and breast pCR rates were comparable between treatment groups regardless of age, region, or clinical stage. Overall, 47.6% (CT-P6) and 52.2% (trastuzumab) of patients experienced study drug-related treatment-emergent adverse events (TEAEs), including 17 patients reporting heart failure (CT-P6: 10; trastuzumab: 7). Two CT-P6 and three trastuzumab patients discontinued adjuvant treatment due to TEAEs.

Conclusion: Adjuvant CT-P6 demonstrated comparable efficacy and safety to trastuzumab at 1 year in patients with HER2-positive EBC, supporting CT-P6 and trastuzumab comparability.

Keywords: Adjuvant; Biosimilar; Breast cancer; CT-P6; HER2 positive; Trastuzumab.

Conflict of interest statement

FJE has received personal fees from Celltrion during the conduct of this study and personal fees from Celltrion, Genentech/Roche, Novartis, and Pfizer outside of the submitted work. YB, VB, and AE have received grants from Celltrion during the conduct of this study. YB has also received non-financial support from Roche and Pfizer outside of the submitted work, and personal fees from Roche outside of the submitted work. AE has also received grants from Roche during the conduct of this study and grants from AstraZeneca and Pfizer outside of the submitted work. SJL, SYL, and SYY are employees of CELLTRION, Inc. In 2018 - present Professor Stebbing, the Editor-in-Chief of Oncogene sat on scientific advisory boards for Celltrion, Singapore Biotech, Vor Biopharma, TLC Biopharmaceuticals and Benevolent AI, has consulted with Lansdowne partners, Vitruvian and Social Impact Capital and he Chairs the Board of Directors for BB Biotech Healthcare Trust and Xerion Healthcare. AM, VM, GD, EZ, DB, DS, JP, RKL, AR, and BT have nothing to disclose.

Figures

Fig. 1
Fig. 1
Patient flow diagram. aOne patient each from the CT-P6 and trastuzumab treatment groups completed the neoadjuvant period, underwent surgery, and initiated the adjuvant period, but did not complete pCR assessment due to lost pathological samples. bDue to relocation (n = 1) and due to being unable to visit treatment site within the visit window (n = 1). GCP good clinical practice, pCR pathological complete response
Fig. 2
Fig. 2
Overall significant decrease in left ventricular ejection fraction. aIf LVEF decreased by ten ejection fraction points from baseline and decreased below an absolute value of 50%, LVEF decrease was confirmed by reassessment within 3 weeks to consider treatment discontinuation. LVEF left ventricular ejection fraction

References

    1. Buzdar AU, Valero V, Ibrahim NK, Francis D, Broglio KR, Theriault RL, Pusztai L, Green MC, Singletary SE, Hunt KK, Sahin AA, Esteva F, Symmans WF, Ewer MS, Buchholz TA, Hortobagyi GN. Neoadjuvant therapy with paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide chemotherapy and concurrent trastuzumab in human epidermal growth factor receptor 2-positive operable breast cancer: an update of the initial randomized study population and data of additional patients treated with the same regimen. Clin Cancer Res. 2007;13(1):228–233. doi: 10.1158/1078-0432.ccr-06-1345.
    1. Gianni L, Eiermann W, Semiglazov V, Lluch A, Tjulandin S, Zambetti M, Moliterni A, Vazquez F, Byakhov MJ, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Magazzù D, Heinzmann D, Steinseifer J, Valagussa P, Baselga J. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014;15(6):640–647. doi: 10.1016/S1470-2045(14)70080-4.
    1. 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, Lauer S, McFadden E, Leyland-Jones B, Bell R, Dowsett M, Jackisch C. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389(10075):1195–1205. doi: 10.1016/S0140-6736(16)32616-2.
    1. Lammers P, Criscitiello C, Curigliano G, Jacobs I. Barriers to the use of trastuzumab for HER2 + breast cancer and the potential impact of biosimilars: a physician survey in the United States and emerging markets. Pharmaceuticals. 2014;7(9):943–953. doi: 10.3390/ph7090943.
    1. United States Food and Drug Administration (2015) Scientific considerations in demonstrating biosimilarity to a reference product: guidance for industry. . Accessed 9 Aug 2019
    1. Esteva FJ, Stebbing J, Wood-Horrall RN, Winkle PJ, Lee SY, Lee SJ. A randomised trial comparing the pharmacokinetics and safety of the biosimilar CT-P6 with reference trastuzumab. Cancer Chemother Pharmacol. 2018;81(3):505–514. doi: 10.1007/s00280-017-3510-7.
    1. Stebbing J, Baranau Y, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, Zhavrid E, Boliukh D, Stroyakovskii D, Pikiel J, Eniu A, Komov D, Morar-Bolba G, Li RK, Rusyn A, Lee SJ, Lee SY, Esteva FJ. CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial. Lancet Oncol. 2017;18(7):917–928. doi: 10.1016/S1470-2045(17)30434-5.
    1. Baselga J, Perez EA, Pienkowski T, Bell R. Adjuvant trastuzumab: a milestone in the treatment of HER-2-positive early breast cancer. Oncologist. 2006;11(suppl 1):4–12. doi: 10.1634/theoncologist.11-90001-4.
    1. 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, Hoss C, Kahlert S, Beck T, Fett W, Mehta KM, von Minckwitz G, Loibl S. 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. 2011;29(25):3351–3357. doi: 10.1200/jco.2010.31.4930.
    1. Hamy-Petit A-S, Belin L, Bonsang-Kitzis H, Paquet C, Pierga J-Y, Lerebours F, Cottu P, Rouzier R, Savignoni A, Lae M, Reyal F. Pathological complete response and prognosis after neoadjuvant chemotherapy for HER2-positive breast cancers before and after trastuzumab era: results from a real-life cohort. Br J Cancer. 2016;114(1):44–52. doi: 10.1038/bjc.2015.426.
    1. Buzatto IPC, Ribeiro-Silva A, Andrade JM, Carrara HHA, Silveira WA, Tiezzi DG. Neoadjuvant chemotherapy with trastuzumab in HER2-positive breast cancer: pathologic complete response rate, predictive and prognostic factors. Braz J Med Biol Res. 2017;50(2):e5674. doi: 10.1590/1414-431X20165674.
    1. Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S, Zambetti M, Vazquez F, Byakhow M, Lichinitser M, Climent MA, Ciruelos E, Ojeda B, Mansutti M, Bozhok A, Baronio R, Feyereislova A, Barton C, Valagussa P, Baselga J. 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. 2010;375(9712):377–384. doi: 10.1016/S0140-6736(09)61964-4.
    1. Suter TM, Procter M, van Veldhuisen DJ, Muscholl M, Bergh J, Carlomagno C, Perren T, Passalacqua R, Bighin C, Klijn JG, Ageev FT, Hitre E, Groetz J, Iwata H, Knap M, Gnant M, Muehlbauer S, Spence A, Gelber RD, Piccart-Gebhart MJ. Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial. J Clin Oncol. 2007;25(25):3859–3865. doi: 10.1200/jco.2006.09.1611.
    1. Hall PS, Hulme C, McCabe C, Oluboyede Y, Round J, Cameron DA. Updated cost-effectiveness analysis of trastuzumab for early breast cancer. Pharmacoeconomics. 2011;29(5):415–432. doi: 10.2165/11588340-000000000-00000.
    1. Aboutorabi A, Hadian M, Ghaderi H, Salehi M, Ghiasipour M. Cost-effectiveness analysis of trastuzumab in the adjuvant treatment for early breast cancer. Glob J Health Sci. 2015;7(1):98–106. doi: 10.5539/gjhs.v7n1p98.

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