Skip to main content
Top
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Breast Cancer | Research article

Trastuzumab use in older patients with HER2-positive metastatic breast cancer: outcomes and treatment patterns in a whole-of-population Australian cohort (2003–2015)

Authors: Benjamin Daniels, Belinda E. Kiely, Monica Tang, Hanna Tervonen, Sallie-Anne Pearson

Published in: BMC Cancer | Issue 1/2019

Login to get access

Abstract

Background

Older patients with HER2-positive metastatic breast (HER2 + MBC) cancer are underrepresented in clinical trials. We aim to describe the treatment patterns and overall survival (OS) for older women receiving trastuzumab for HER2 + MBC.

Methods

Retrospective, whole-of-population cohort study using demographic, dispensing, and medical services data for Australian women ≥ 65 years initiating trastuzumab for HER2 + MBC between 2003 and 2015. We describe time-on-trastuzumab; type and timing of other cancer treatments; rates of cardiac monitoring; and OS from trastuzumab initiation for HER2 + MBC.

Results

Of 5404 women initiating trastuzumab for HER2 + MBC, 1583 (29%) were ≥ 65 years old, and the proportion of older patients increased from 20% in 2003 to 38% in 2015. The median age for older women was 73 years and 516 (33%) were ≥ 75 years. Most older patients (92%) received ≥3medicines for comorbidities other than cancer. Median (IQR) time on trastuzumab was 14.1 months (5.9–32.1) and on all chemotherapy was 5.6 months (3.3–10.8). 74% received ≥1 chemotherapy agent and 56% received endocrine therapy. Half (49%) of patients had a cardiac assessment prior to initiating trastuzumab and overall 1228 (76%) had ≥1 cardiac assessment during the study period. At a median follow-up of 6 years, 73% of patients had died and the median OS was 25.6 months (IQR 10.7–58.7).

Conclusions

Older patients comprise a growing proportion of patients treated with HER2-targeted therapies in the real-world but they remain underrepresented in trials of these agents. Few trials report duration or OS estimates for older patients but our estimates are similar to those from trials that have. Although cardiac monitoring was a requirement of accessing trastuzumab during our study period, many patients did not undergo a cardiac assessment.
Appendix
Available only for authorised users
Literature
1.
go back to reference Rawlins M. De testimonio: on the evidence for decisions about the use of therapeutic interventions. Lancet. 2008;372(9656):2152–61.CrossRef Rawlins M. De testimonio: on the evidence for decisions about the use of therapeutic interventions. Lancet. 2008;372(9656):2152–61.CrossRef
2.
go back to reference van de Water W, Kiderlen M, Bastiaannet E, Siesling S, Westendorp RG, van de Velde CJ, et al. External validity of a trial comprised of elderly patients with hormone receptor-positive breast cancer. J Natl Cancer Inst. 2014;106(4):dju051.CrossRef van de Water W, Kiderlen M, Bastiaannet E, Siesling S, Westendorp RG, van de Velde CJ, et al. External validity of a trial comprised of elderly patients with hormone receptor-positive breast cancer. J Natl Cancer Inst. 2014;106(4):dju051.CrossRef
5.
go back to reference Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.CrossRef Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7–30.CrossRef
6.
go back to reference Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med. 1999;341(27):2061–7.CrossRef Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med. 1999;341(27):2061–7.CrossRef
7.
go back to reference Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–92.CrossRef Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–92.CrossRef
8.
go back to reference Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724–34.CrossRef Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724–34.CrossRef
9.
go back to reference Miles D, Baselga J, Amadori D, Sunpaweravong P, Semiglazov V, Knott A, et al. Treatment of older patients with HER2-positive metastatic breast cancer with pertuzumab, trastuzumab, and docetaxel: subgroup analyses from a randomized, double-blind, placebo-controlled phase III trial (CLEOPATRA). Breast Cancer Res Treat. 2013;142(1):89–99.CrossRef Miles D, Baselga J, Amadori D, Sunpaweravong P, Semiglazov V, Knott A, et al. Treatment of older patients with HER2-positive metastatic breast cancer with pertuzumab, trastuzumab, and docetaxel: subgroup analyses from a randomized, double-blind, placebo-controlled phase III trial (CLEOPATRA). Breast Cancer Res Treat. 2013;142(1):89–99.CrossRef
10.
go back to reference Fyfe G, Mass R, Murphy M, Slamon D. Older (age > 60 years) patients obtain survival benefit from herceptin plus chemotherapy. Eur J Cancer. 2001;37:S189–S90.CrossRef Fyfe G, Mass R, Murphy M, Slamon D. Older (age > 60 years) patients obtain survival benefit from herceptin plus chemotherapy. Eur J Cancer. 2001;37:S189–S90.CrossRef
11.
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(2):109–19.CrossRef 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(2):109–19.CrossRef
12.
go back to reference Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, et al. Trastuzumab Emtansine with or without Pertuzumab versus Trastuzumab plus Taxane for human epidermal growth factor receptor 2-positive, advanced breast Cancer: primary results from the phase III MARIANNE study. J Clin Oncol. 2017;35(2):141–8.CrossRef Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, et al. Trastuzumab Emtansine with or without Pertuzumab versus Trastuzumab plus Taxane for human epidermal growth factor receptor 2-positive, advanced breast Cancer: primary results from the phase III MARIANNE study. J Clin Oncol. 2017;35(2):141–8.CrossRef
13.
go back to reference Krop IE, Kim SB, Martin AG, LoRusso PM, Ferrero JM, Badovinac-Crnjevic 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(6):743–54.CrossRef Krop IE, Kim SB, Martin AG, LoRusso PM, Ferrero JM, Badovinac-Crnjevic 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(6):743–54.CrossRef
14.
go back to reference Daste A, Chakiba C, Domblides C, Gross-goupil M, Quivy A, Ravaud A, et al. Targeted therapy and elderly people: a review. Eur J Cancer. 2016;69:199–215.CrossRef Daste A, Chakiba C, Domblides C, Gross-goupil M, Quivy A, Ravaud A, et al. Targeted therapy and elderly people: a review. Eur J Cancer. 2016;69:199–215.CrossRef
16.
go back to reference Lu CY, Barratt J, Vitry A, Roughead E. Charlson and Rx-risk comorbidity indices were predictive of mortality in the Australian health care setting. J Clin Epidemiol. 2011;64(2):223–8.CrossRef Lu CY, Barratt J, Vitry A, Roughead E. Charlson and Rx-risk comorbidity indices were predictive of mortality in the Australian health care setting. J Clin Epidemiol. 2011;64(2):223–8.CrossRef
17.
go back to reference Mellish L, Karanges EA, Litchfield MJ, Schaffer AL, Blanch B, Daniels BJ, et al. The Australian pharmaceutical benefits scheme data collection: a practical guide for researchers. BMC Res Notes. 2015;8(1):634.CrossRef Mellish L, Karanges EA, Litchfield MJ, Schaffer AL, Blanch B, Daniels BJ, et al. The Australian pharmaceutical benefits scheme data collection: a practical guide for researchers. BMC Res Notes. 2015;8(1):634.CrossRef
18.
go back to reference Daniels B, Kiely BE, Lord SJ, Houssami N, Lu CY, Ward RL, et al. Trastuzumab for metastatic breast cancer: Real world outcomes from an Australian whole-of-population cohort (2001–2016). Breast. 2017;38:7–13.CrossRef Daniels B, Kiely BE, Lord SJ, Houssami N, Lu CY, Ward RL, et al. Trastuzumab for metastatic breast cancer: Real world outcomes from an Australian whole-of-population cohort (2001–2016). Breast. 2017;38:7–13.CrossRef
19.
go back to reference Daniels B, Kiely BE, Lord SJ, Houssami N, Lu CY, Ward RL, et al. Long-term survival in trastuzumab-treated patients with HER2-positive metastatic breast cancer: real-world outcomes and treatment patterns in a whole-of-population Australian cohort (2001–2016). Breast Cancer Res Treat. 2018;171:151–9.CrossRef Daniels B, Kiely BE, Lord SJ, Houssami N, Lu CY, Ward RL, et al. Long-term survival in trastuzumab-treated patients with HER2-positive metastatic breast cancer: real-world outcomes and treatment patterns in a whole-of-population Australian cohort (2001–2016). Breast Cancer Res Treat. 2018;171:151–9.CrossRef
20.
go back to reference Pearson SA, Ringland CL, Ward RL. Trastuzumab and metastatic breast cancer: trastuzumab use in Australia--monitoring the effect of an expensive medicine access program. J Clin Oncol. 2007;25(24):3688–93.CrossRef Pearson SA, Ringland CL, Ward RL. Trastuzumab and metastatic breast cancer: trastuzumab use in Australia--monitoring the effect of an expensive medicine access program. J Clin Oncol. 2007;25(24):3688–93.CrossRef
21.
go back to reference Zeng C, Wen W, Morgans AK, Pao W, Shu XO, Zheng W. Disparities by race, age, and sex in the improvement of survival for major cancers: results from the National Cancer Institute surveillance, epidemiology, and end results (SEER) program in the United States, 1990 to 2010. JAMA Oncol. 2015;1(1):88–96.CrossRef Zeng C, Wen W, Morgans AK, Pao W, Shu XO, Zheng W. Disparities by race, age, and sex in the improvement of survival for major cancers: results from the National Cancer Institute surveillance, epidemiology, and end results (SEER) program in the United States, 1990 to 2010. JAMA Oncol. 2015;1(1):88–96.CrossRef
22.
go back to reference Foukakis T, Fornander T, Lekberg T, Hellborg H, Adolfsson J, Bergh J. Age-specific trends of survival in metastatic breast cancer: 26 years longitudinal data from a population-based cancer registry in Stockholm, Sweden. Breast Cancer Res Treat. 2011;130(2):553–60.CrossRef Foukakis T, Fornander T, Lekberg T, Hellborg H, Adolfsson J, Bergh J. Age-specific trends of survival in metastatic breast cancer: 26 years longitudinal data from a population-based cancer registry in Stockholm, Sweden. Breast Cancer Res Treat. 2011;130(2):553–60.CrossRef
23.
go back to reference Ruiterkamp J, Ernst MF, de Munck L, van der Heiden-van der Loo M, Bastiaannet E, van de Poll-Franse LV, et al. Improved survival of patients with primary distant metastatic breast cancer in the period of 1995-2008. A nationwide population-based study in the Netherlands. Breast Cancer Res Treat. 2011;128(2):495–503.CrossRef Ruiterkamp J, Ernst MF, de Munck L, van der Heiden-van der Loo M, Bastiaannet E, van de Poll-Franse LV, et al. Improved survival of patients with primary distant metastatic breast cancer in the period of 1995-2008. A nationwide population-based study in the Netherlands. Breast Cancer Res Treat. 2011;128(2):495–503.CrossRef
24.
go back to reference Jackisch C, Schoenegg W, Reichert DA, Welslau M, Selbach J, Harich H-D, et al. Long-term results on trastuzumab (T) in elderly patients (EP) with locally advanced or metastatic HER2-positive breast cancer (BC). J Clin Oncol. 2014;32(15_suppl):624.CrossRef Jackisch C, Schoenegg W, Reichert DA, Welslau M, Selbach J, Harich H-D, et al. Long-term results on trastuzumab (T) in elderly patients (EP) with locally advanced or metastatic HER2-positive breast cancer (BC). J Clin Oncol. 2014;32(15_suppl):624.CrossRef
25.
go back to reference Kaufman PA, Brufsky AM, Mayer M, Rugo HS, Tripathy D, Yood MU, et al. Treatment patterns and clinical outcomes in elderly patients with HER2-positive metastatic breast cancer from the registHER observational study. Breast Cancer Res Treat. 2012;135(3):875–83.CrossRef Kaufman PA, Brufsky AM, Mayer M, Rugo HS, Tripathy D, Yood MU, et al. Treatment patterns and clinical outcomes in elderly patients with HER2-positive metastatic breast cancer from the registHER observational study. Breast Cancer Res Treat. 2012;135(3):875–83.CrossRef
26.
go back to reference Denegri A, Moccetti T, Moccetti M, Spallarossa P, Brunelli C, Ameri P. Cardiac toxicity of trastuzumab in elderly patients with breast cancer. J Geriatr Cardiol. 2016;13(4):355–63.PubMedPubMedCentral Denegri A, Moccetti T, Moccetti M, Spallarossa P, Brunelli C, Ameri P. Cardiac toxicity of trastuzumab in elderly patients with breast cancer. J Geriatr Cardiol. 2016;13(4):355–63.PubMedPubMedCentral
27.
go back to reference Lu CY, Srasuebkul P, Drew AK, Ward RL, Pearson SA. Positive spillover effects of prescribing requirements: increased cardiac testing in patients treated with trastuzumab for HER2+ metastatic breast cancer. Intern Med J. 2012;42(11):1229–35.CrossRef Lu CY, Srasuebkul P, Drew AK, Ward RL, Pearson SA. Positive spillover effects of prescribing requirements: increased cardiac testing in patients treated with trastuzumab for HER2+ metastatic breast cancer. Intern Med J. 2012;42(11):1229–35.CrossRef
Metadata
Title
Trastuzumab use in older patients with HER2-positive metastatic breast cancer: outcomes and treatment patterns in a whole-of-population Australian cohort (2003–2015)
Authors
Benjamin Daniels
Belinda E. Kiely
Monica Tang
Hanna Tervonen
Sallie-Anne Pearson
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-6126-y

Other articles of this Issue 1/2019

BMC Cancer 1/2019 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