Skip to main content
Top
Published in: Breast Cancer 4/2019

Open Access 01-07-2019 | Breast Cancer | Original Article

Comparison of the efficacy of trastuzumab emtansine between patients with metastatic human epidermal growth factor receptor 2-positive breast cancers previously treated with combination trastuzumab and pertuzumab and with trastuzumab only in Japanese population

Authors: Shoko Noda-Narita, Akihiko Shimomura, Asuka Kawachi, Hitomi Sumiyoshi-Okuma, Kazuki Sudo, Tatsunori Shimoi, Emi Noguchi, Kan Yonemori, Chikako Shimizu, Yasuhiro Fujiwara, Kenji Tamura

Published in: Breast Cancer | Issue 4/2019

Login to get access

Abstract

Background

Trastuzumab emtansine (T-DM1) has been approved since 2013 for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) who had received trastuzumab (Tmab) and taxane. However, no clinical trial has evaluated the efficacy of T-DM1 in those who have previously received pertuzumab (Pmab). This study aimed to compare the efficacy of T-DM1 between patients who had received Tmab and Pmab and those who had received Tmab only in Japanese population.

Methods

We identified all patients with HER2-positive MBC who received T-DM1 between April 1, 2014 and February 28, 2017 in our institution. The patients were divided into the Tmab group (i.e., those who received only Tmab before T-DM1 treatment) and the Tmab/Pmab group (i.e., those who received Tmab and Pmab before T-DM1 treatment), and progression-free survival (PFS) and best response were compared between the two groups.

Results

A total of 42 patients were enrolled for outcome analysis. The median follow-up period was 4.8 months, and the median number of prior chemotherapy regimens for metastatic disease before T-DM1 was 1 (range 1–2) in the Tmab/Pmab group and 2 (range 0–6) in the Tmab group. The median PFS was 2.8 months in the Tmab/Pmab group (95% confidence interval [CI] 1.7–4.8 months) and 7.8 months in the Tmab group (95% CI 5.5–15.9 months) (p = 0.0030). The best response was lower in the Tmab/Pmab group (11.1% vs. 25.0%).

Conclusions

Patients with HER2-positive MBC who received Tmab and Pmab treatment before T-DM1 have fewer benefits from T-DM1.
Literature
1.
go back to reference Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367:1783–91.CrossRefPubMedPubMedCentral Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367:1783–91.CrossRefPubMedPubMedCentral
2.
go back to reference Dieras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18:732–42.CrossRefPubMedPubMedCentral Dieras V, Miles D, Verma S, Pegram M, Welslau M, Baselga J, et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18:732–42.CrossRefPubMedPubMedCentral
3.
go back to reference Krop IE, Kim SB, Gonzalez-Martin A, LoRusso PM, Ferrero JM, Smitt M, 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;15:689–99.CrossRefPubMed Krop IE, Kim SB, Gonzalez-Martin A, LoRusso PM, Ferrero JM, Smitt M, 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;15:689–99.CrossRefPubMed
4.
go back to reference Krop IE, Kim SB, Martin AG, LoRusso PM, Ferrero JM, Badovinac-Cmjevic T, et al. Trastuzumab emtansine versus treatment of physician’s choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial. Lancet Oncol. 2017;18:743–54.CrossRefPubMed Krop IE, Kim SB, Martin AG, LoRusso PM, Ferrero JM, Badovinac-Cmjevic T, et al. Trastuzumab emtansine versus treatment of physician’s choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial. Lancet Oncol. 2017;18:743–54.CrossRefPubMed
5.
go back to reference Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366:109–19.CrossRefPubMed Baselga J, Cortes J, Kim SB, Im SA, Hegg R, Im YH, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366:109–19.CrossRefPubMed
6.
go back to reference Swain SM, Kim SB, Cortes J, Ro J, Semiglazov V, Campone M, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013;14:461–71.CrossRefPubMedPubMedCentral Swain SM, Kim SB, Cortes J, Ro J, Semiglazov V, Campone M, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013;14:461–71.CrossRefPubMedPubMedCentral
7.
go back to reference Dzimitrowicz H, Berger M, Vargo C, Hood A, Abdelghany O, Raghavendra AS, et al. T-DM1 activity in metastatic human epidermal growth factor receptor 2-positive breast cancers that received prior therapy with trastuzumab and pertuzumab. J Clin Oncol. 2016;34:3511–7.CrossRefPubMedPubMedCentral Dzimitrowicz H, Berger M, Vargo C, Hood A, Abdelghany O, Raghavendra AS, et al. T-DM1 activity in metastatic human epidermal growth factor receptor 2-positive breast cancers that received prior therapy with trastuzumab and pertuzumab. J Clin Oncol. 2016;34:3511–7.CrossRefPubMedPubMedCentral
8.
go back to reference de Melo Galiato D, Jardim DL, Marchesi MS, Hortobagyi GN. Mechanisms of resistance and sensitivity of anti-HER2 therapies in HER2+ breast cancer. Oncotarget. 2016;7:64431–46. de Melo Galiato D, Jardim DL, Marchesi MS, Hortobagyi GN. Mechanisms of resistance and sensitivity of anti-HER2 therapies in HER2+ breast cancer. Oncotarget. 2016;7:64431–46.
10.
go back to reference Phillips GD, Fields CT, Li G, Dowbenko D, Schaefer G, Miller K, et al. Dual targeting of HER2-positive cancer with trastuzumab emtansine and pertuzumab: critical role for neuregulin blockade in antitumor response to combination therapy. Clin Cancer Res. 2014;20:456–68.CrossRefPubMed Phillips GD, Fields CT, Li G, Dowbenko D, Schaefer G, Miller K, et al. Dual targeting of HER2-positive cancer with trastuzumab emtansine and pertuzumab: critical role for neuregulin blockade in antitumor response to combination therapy. Clin Cancer Res. 2014;20:456–68.CrossRefPubMed
11.
go back to reference Holbro T, Beerli RR, Maurer F, Koziczak M, Barbas CF 3rd, Hynes NE. The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc Natl Acad Sci USA. 2003;100:8933–8.CrossRefPubMedPubMedCentral Holbro T, Beerli RR, Maurer F, Koziczak M, Barbas CF 3rd, Hynes NE. The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc Natl Acad Sci USA. 2003;100:8933–8.CrossRefPubMedPubMedCentral
12.
go back to reference Hutcheson I, Borrow D, Hasmann M, Nicholson R. Induction of erbB3/EGFR heterodimers mediates resistance to pertuzumab in a tamoxifen-resistant MCF-7 breast cancer cell line. Mol Cancer Ther. 2007;6:3373S. Hutcheson I, Borrow D, Hasmann M, Nicholson R. Induction of erbB3/EGFR heterodimers mediates resistance to pertuzumab in a tamoxifen-resistant MCF-7 breast cancer cell line. Mol Cancer Ther. 2007;6:3373S.
13.
go back to reference Vici P, Pizzuti L, Michelotti A, Sperduti I, Natoli C, Mentuccia L, et al. A retrospective multicentric observational study of tratuzumab emstasine in HER2 positive metastatic breast cancer: a real-world experience. Oncotarget. 2017;8:56921–31.CrossRefPubMedPubMedCentral Vici P, Pizzuti L, Michelotti A, Sperduti I, Natoli C, Mentuccia L, et al. A retrospective multicentric observational study of tratuzumab emstasine in HER2 positive metastatic breast cancer: a real-world experience. Oncotarget. 2017;8:56921–31.CrossRefPubMedPubMedCentral
14.
go back to reference Fabi A, Giannarelli D, Moscetti L, Santini D, Zambelli A, Laurentiis M, et al. Ado-trastuzumab emtansine (T-DM1) in HER2+ advanced breast cancer patients: does pretreatment wht pertuzumab matter? Future Oncol. 2017;13:2791–7.CrossRefPubMed Fabi A, Giannarelli D, Moscetti L, Santini D, Zambelli A, Laurentiis M, et al. Ado-trastuzumab emtansine (T-DM1) in HER2+ advanced breast cancer patients: does pretreatment wht pertuzumab matter? Future Oncol. 2017;13:2791–7.CrossRefPubMed
Metadata
Title
Comparison of the efficacy of trastuzumab emtansine between patients with metastatic human epidermal growth factor receptor 2-positive breast cancers previously treated with combination trastuzumab and pertuzumab and with trastuzumab only in Japanese population
Authors
Shoko Noda-Narita
Akihiko Shimomura
Asuka Kawachi
Hitomi Sumiyoshi-Okuma
Kazuki Sudo
Tatsunori Shimoi
Emi Noguchi
Kan Yonemori
Chikako Shimizu
Yasuhiro Fujiwara
Kenji Tamura
Publication date
01-07-2019
Publisher
Springer Japan
Published in
Breast Cancer / Issue 4/2019
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-019-00949-4

Other articles of this Issue 4/2019

Breast Cancer 4/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine