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Breast cancer, early stage

1269 - Neoadjuvant therapy with trastuzumab emtansine and pertuzumab in patients with HER2-positive primary breast cancer (A randomized, phase 2 study; JBCRG-20)


09 Sep 2017


Breast cancer, early stage


Cytotoxic Therapy;  Breast Cancer


Norikazu Masuda


Annals of Oncology (2017) 28 (suppl_5): v43-v67. 10.1093/annonc/mdx362


N. Masuda1, S. Ohtani2, T. Takano3, K. Inoue4, E. Suzuki5, R. Nakamura6, H. Bando7, Y. Ito8, K. Ishida9, T. Yamanaka10, K. Kuroi11, H. Yasojima1, H. Kasai12, T. Takasuka13, T. Sakurai14, T.R. Kataoka14, S. Morita15, S. Ohno16, M. Toi17

Author affiliations

  • 1 Department Of Surgery, Breast Oncology, NHO Osaka National Hospital, 540-0006 - Osaka/JP
  • 2 Department Of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital, 730-8618 - Hiroshima/JP
  • 3 Department Of Medical Oncology, Toranomon Hospital, 105-8470 - Tokyo/JP
  • 4 Division Of Breast Oncology, Saitama Cancer Center, 362-0806 - Saitama/JP
  • 5 Department Of Breast Surgery, Kyoto University, Kyoto/JP
  • 6 Department Of Breast Surgery, Chiba Cancer Center, 260-8717 - Chiba/JP
  • 7 Breast And Endocrine Surgery, Faculty Of Medicine, University of Tsukuba, 305-8577 - Tsukuba/JP
  • 8 Breast Medical Oncology Department, The Cancer Institute Hospital of JFCR, 135-8550 - Tokyo/JP
  • 9 Department Of Surgery, Iwate Medical University, Morioka/JP
  • 10 Breast And Endocrine Surgery, Kanagawa Cancer Center, Yokohama/JP
  • 11 Breast Surgery, Tokyo Metropolitan Health and Medical Treatment Corporation Ebara Hospital, Tokyo/JP
  • 12 Institute For Advancement Of Clinical And Translational Science (iact), Kyoto University Hospital, Kyoto/JP
  • 13 Oncology Lifecycle Management, Chugai Pharmaceutical, Tokyo/JP
  • 14 Department Of Diagnostic Pathology, Kyoto University Hospital, Kyoto/JP
  • 15 Department Of Biomedical Statistics And Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto/JP
  • 16 Breast Oncology Center, The Cancer Institute Hospital of JFCR, 135-8550 - Tokyo/JP
  • 17 Department Of Surgery (breast Surgery), Kyoto University Graduate School of Medicine, 606-8507 - Kyoto/JP


Abstract 1269


Exploration of neoadjuvant chemotherapy with anti-HER2 therapy to achieve higher pathological complete response (pCR) is important. We focused on trastuzumab emtansine (T-DM1), pertuzumab (P) and tailored response guided therapy in HER2+ primary breast cancer (cT1c–T3, cN0–N1, M0, tumor ≤ 7 cm).


This randomized phase II study evaluated efficacy and safety of 3 regimens, A) 6 cycles TCbHP, B) 4 cycles TCbHP followed by 4 cycles T-DM1+P, and C) 6 cycles T-DM1+P: responders to 4 cycles T-DM1+P were assigned to 2 more cycles [C1] or non-responders were assigned to 4 cycles FEC [C2] (Table). Responders: ≥30% decrease in tumor size (MRI) and Ki67 ≤10% or no cancer cells in core needle biopsy. ER(+) patients received anti-hormonal therapy concurrent to T-DM1+P. HER2, ER and Ki-67 were assessed in a central laboratory. Primary endpoint was pCR rate (yT0-is, yN0; centrally confirmed). Secondary endpoints were safety, ORR and breast conservation rate.


A total of 206 patients were enrolled (Aug 2014-Feb 2016; full analysis set, n = 204). Patient characteristics were comparable among all groups (median age 53.0 y, post-menopause 53.9%, T2 70.6%, median tumor size 26 mm, N0 63.2%, ER(+) 57.8%). In group C, 80 (79.2%) patients continued T-DM1+P due to favorable response. pCR rate in group A, B, and C was 56.9%, 71.2%, and 57.4%. By exploratory analyses, pCR rate was higher for groups B and C1 than A in ER(+), but comparable in ER(-) patients. No significant differences in secondary endpoints. No treatment discontinuation due to AEs and similar drug-related SAE profile were seen among groups. Of specific mention: low drug-related alopecia in group C1 (5.0%) than A, B or C2 (81%–94%) and less febrile neutropenia in C1 (0%) than A, B or C2 (15%–33%).Table:

159PD Summary of response

Variable Group A (6-cycle TCbHP) % (n = 51) Group B (4-cycle TCbHP switched to 4-cycle T-DM1+P) % (n = 52) Group C1 (4-cycle T-DM1+P continued 2-cycle T-DM1+P) % (n = 80) Group C2 (4-cycle T-DM1+P switched to 4-cycle FEC) % (n = 21) Group C % (n = 101)
pCR rate, Overall 56.9 (29/51) 71.2 (37/52) 62.5 (50/80) 38.1 (8/21) 57.4 (58/101)
pCR rate, ER (-) 76.2 (16/21) 73.9 (17/23) 72.2 (26/36) 33.3 (2/6) 66.7 (28/42)
pCR rate, ER (+) 43.3 (13/30) 69.0 (20/29) 54.5 (24/44) 40.0 (6/15) 50.8 (30/59)
ORR 96.1 (49/51) 86.5 (45/52) 88.8 (71/80) 85.7 (18/21) 88.1 (89/101)
cCR 47.1 (24/51) 51.9 (27/52) 38.8 (31/80) 38.1 (8/21) 38.6 (39/101)
Breast conservation rate 52.0 (26/50) 51.9 (27/52) 54.4 (43/79) 38.1 (8/21) 51.0 (51/100)
Breast conservation rate from planned mastectomy 34.4 (11/32) 38.7 (12/31) 36.7 (18/49) 14.3 (2/14) 31.7 (20/63)

Dose was administered every 3 weeks as adjuvant therapy. ER (+) patients received concurrent endocrine therapy during T-DM1 treatment. ER, estrogen receptor; FEC, 5-fluorouracil/epirubicin/cyclophosphamide; ORR, overall response rate; pCR, pathological complete response; TCbHP, docetaxel/carboplatin/trastuzumab + pertuzumab; T-DM1+P, trastuzumab emtansine + pertuzumab


Addition of T-DM1+P to standard TCbHP regimen may be possibly superior to TCbHP. Tailored T-DM1+P is a promising approach with mostly equal efficacy and less toxicity compared to TCbHP.

Clinical trial identification

UMIN-CTR: UMIN000014649

Legal entity responsible for the study

Japan Breast Cancer Research Group


Japan Breast Cancer Research Group and Chugai Pharmaceutical Co., Ltd.


N. Masuda: Honorarium from Chugai and AstraZeneca. T. Takano, M. Toi: Funding from Chugai. Y. Ito: Funding from MSD, AstraZeneca, Novartis, Parexel, Chugai, and Lilly. H. Kasai: Consulting fee/honorarium from Chugai. T. Takasuka: Employee and stock options with Chugai. S. Morita: Consultancy for Chugai. All other authors have declared no conflicts of interest.

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