Postneoadjuvant therapy: a new approach to the treatment of HER2-positive breast cancer (KATHERINE study results)
https://doi.org/10.21518/2079-701X-2019-19-44-49
Abstract
Up until recently, neoadjuvant and adjuvant treatment regimens for breast cancer (BC) were considered equivalent in their effect on long-term treatment outcomes. Despite the fact that additional information on the prognosis of patients (achievement or failure to achieve complete drug pathomorphosis) was obtained during neoadjuvant therapy, we could not change this prognosis, since there was no evidence that any variant of adjuvant therapy could improve survival of patients, who did not achieve complete morphological tumour regression. In December 2018, investigators presented the results of the first planned interim analysis of invasive disease-free survival (iDFS) of patients with early HER2-positive breast cancer, who had residual tumour after neoadjuvant anti-HER2-containing therapy, depending on the adjuvant treatment option: either trastuzumab emtansine (n = 743) or trastuzumab (n = 743). The expected 3-year iDFS in patients, who received trastuzumab emtansine as adjuvant therapy, was 88.3%, while that in the standard trastuzumab group accounted for only 77% (RR = 0.50; 95% CI 0.39–0, 64; h <0.001). The results of the KATHERINE study, which showed an improvement in the survival rates of patients with HER2-positive breast cancer, who did not achieve complete therapeutic pathomorphism (pCR) against the background of neoadjuvant anti-HER2 therapy with the use of trastuzumab emtansine in the adjuvant mode, are not just an important milestone in the treatment of HER2-positive breast cancer. These results reverse the attitude towards neoadjuvant therapy, as we were able, for the first time, to improve the treatment outcome due to the change of the therapy based on therapeutic pathomorphosis data. Thus, this approach leads to the fact that neoadjuvant therapy becomes a more effective technique, at least in HER2-positive breast cancer.
About the Authors
L. G. Zhukova
State Budgetary Health Institution of the city of Moscow «Loginov Moscow Clinical Research Center» of Moscow Health Department
Russian Federation
Russian Federation
Dr. of Sci. (Med.), Professor of RAS, Deputy Oncology Director
86 Shosse Entuziastov, Moscow, 111123, Russia
S. A. Smolin
State Budgetary Health Institution of the city of Moscow «Loginov Moscow Clinical Research Center» of Moscow Health Department
Russian Federation
Russian Federation
Junior Researcher, Chemotherapy Department
86 Shosse Entuziastov, Moscow, 111123, Russia
References
1. Susmitha Apuri. Neoadjuvant and Adjuvant Therapies for Breast Cancer. South Med J. 2017;110(10):638-642. doi: 10.14423/SMJ.0000000000000703.
2. Berns K., Horlings H.M., Hennessy B.T., Madiredjo M., Hijmans E.M., Beelen K, et al. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell. 2007;12(4):395-402. doi: 10.1016/j.ccr.2007.08.030.
3. Fabi A., Di Benedetto A., Metro G., Perracchio L., Nisticò C., Di Filippo F., et al. HER2 protein and gene variation between primary and metastatic breast cancer: significance and impact on patient care. Clinical Cancer Research. 2011;17(7):205520-64. doi: 10.1158/1078-0432.CCR-10-1920.
4. von Minckwitz G., Procter M., de Azambuja E., Zardavas D., Benyunes M., et al. APHINITY Steering Committee and Investigators. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med. 2017;377(2):122-131. doi: 10.1056/NEJMoa1703643.
5. Untch M., Fasching P.A., Konecny G.E., Hasmüller S., Lebeau A., Kreienberg R., et al. 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.
6. de Azambuja E., Holmes A.P., Piccart-Gebhart M., Holmes E., Di Cosimo S., Swaby R.F., et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response. Lancet Oncol. 2014;15(10):1137-1146. doi: 10.1016/S1470-2045(14)70320-1.
7. Cardoso F., Kyriakides S., Ohno S., PenaultLlorca F., Poortmans P., Rubio I.T., Zackrisson S., Senkus E. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019. pii: mdz189. doi: 10.1093/annonc/mdz189.
8. Inno A., Barni S., Ghidini A., Zaniboni A., Petrelli F. One year versus a shorter duration of adjuvant trastuzumab for HER2-positive early breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat. 2019;173(2):247-254. doi: 10.1007/s10549-018-5001-x.
9. Zardavas D., Fouad T.M., Piccart M. Optimal adjuvant treatment for patients with HER2-positive breast cancer in 2015. Breast (Edinburgh, Scotland). 2015;24(Suppl 2):143-148. doi: 10.1016/j.breast.2015.07.034.
10. Burris H.A. 3rd, Rugo H.S., Vukelja S.J., Vogel C.L., Borson R.A., Limentani S., et al. Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. J Clin Oncol. 2011;29(4):398-405. doi: 10.1200/JCO.2010.29.5865.
11. Peddi P.F., Hurvitz S.A. Trastuzumab emtansine: the first targeted chemotherapy for treatment of breast cancer. Future Oncol. 2013;9(3):319-326. doi: 10.2217/fon.13.7.
12. Krop I.E., Kim S.B., González-Martín A., LoRusso P.M., Ferrero J.M., Smitt M., Yu R., et al. Trastuzumab emtansine versus treatment of physician’s choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(7):689-699. doi: 10.1016/S1470-2045(14)70178-0.
13. Verma S., Miles D., Gianni L., Krop I.E., Welslau M., Baselga J., et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783-1791. doi: 10.1056/NEJMoa1209124.
14. Penault-Llorca F., Radosevic-Robin N. Biomarkers of residual disease after neoadjuvant therapy for breast cancer. Nature reviews. Clinical oncology. 2016;13(8):487–503. doi: 10.1038/nrclinonc.2016.1.
15. Prowell T.M., Beaver J.A., Pazdur R. Residual Disease after Neoadjuvant Therapy – Developing Drugs for High-Risk Early Breast Cancer. N Engl J Med. 2019;380(7):612-615. doi: 10.1056/NEJMp1900079.
16. Pernas S., Barroso-Sousa R., Tolaney S.M. Optimal treatment of early stage HER2-positive breast cancer. Cancer. 2018;124(23):4455-4466. doi: 10.1002/cncr.31657.
17. Wuerstlein R., Harbeck N. Neoadjuvant Therapy for HER2-positive Breast Cancer. Reviews on recent clinical trials. 2017;12(2):81–92. doi: 10.2174/1574887112666170202165049.
18. Hanusch C., Schneeweiss A., Loibl S., Untch M., Paepke S., Kümmel S., et al. Dual Blockade with AFatinib and Trastuzumab as NEoadjuvant Treatment for Patients with Locally Advanced or Operable Breast Cancer Receiving TaxaneAnthracycline Containing Chemotherapy-DAFNE (GBG-70). Clin Cancer Res. 2015;21(13):2924-2931. doi: 10.1158/1078-0432.CCR-14-2774.
19. Kalous O., Conklin D., Desai A.J., et al. Dacomitinib (PF-00299804), an irreversible Pan-HER inhibitor, inhibits proliferation of HER2-amplified breast cancer cell lines resistant to trastuzumab and lapatinib. Mol Cancer Ther. 2012;11(9):1978-1987. doi: 10.1158/1535-7163.MCT-11-0730.
20. Martin M., Holmes F.A., et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology. 2017;18(12)1688–1700. doi: 10.1016/S1470-2045(17)30717-9.
21. Piccart-Gebhart M., Holmes E., Baselga J., de Azambuja E., Dueck A.C., Viale G., et al. Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial. J Clin Oncol. 2016;34(10):1034-1042. doi: 10.1200/JCO.2015.62.1797.
22. Castaneda S.A., Strasser J. Updates in the Treatment of Breast Cancer with Radiotherapy. Surg Oncol Clin N Am. 2017;26(3):371-382. doi: 10.1016/j.soc.2017.01.013
23. Shah C., Tendulkar R., Smile T., et al. Adjuvant Radiotherapy in Early-Stage Breast Cancer: Evidence-Based Options. Ann Surg Oncol. 2016;23:3880. doi: 10.1245/s10434-016-5503-x.
24. I van Hellemond I.E.G, Geurts S.M.E., TjanHeijnen V.C.G. Current Status of Extended Adjuvant Endocrine Therapy in Early Stage Breast Cancer. Curr Treat Options Oncol. 2018;19(5):26. doi: 10.1007/s11864-018-0541-1.
25. Gourgou-Bourgade S., Cameron D., Poortmans P., Asselain B., Azria D., Cardoso F., et al. Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†. Ann Oncol. 2015;26(5):873-879. doi: 10.1093/annonc/mdv106.
26. Hudis C.A., Barlow W.E., Costantino J.P., Gray R.J., Pritchard K.I., Chapman J.A., et al. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007;25(15):2127-2132. doi: 10.1200/JCO.2006.10.3523.
27. Krop I.E., Suter T.M., Dang C.T., Dirix L., Romieu G., Zamagni C., et al. Feasibility and cardiac safety of trastuzumab emtansine after anthracycline-based chemotherapy as (neo)adjuvant therapy for human epidermal growth factor receptor 2-positive earlystage breast cancer. J Clin Oncol. 2015;33(10):1136-1142. doi: 10.1200/JCO.2014.58.7782.
28. von Minckwitz G., Huang C.S., Mano M.S., Loibl S., Mamounas E.P., Untch M. et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019;380(7):617-628. doi: 10.1056/NEJMoa1814017.
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For citations:
Zhukova LG, Smolin SA. Postneoadjuvant therapy: a new approach to the treatment of HER2-positive breast cancer (KATHERINE study results). Meditsinskiy sovet = Medical Council. 2019;(19):44-50. (In Russ.) https://doi.org/10.21518/2079-701X-2019-19-44-49
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