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Observational Study
. 2025 Jan;209(2):419-430.
doi: 10.1007/s10549-024-07506-4. Epub 2024 Oct 20.

Attrition between lines of therapy and real-world outcomes of patients with HER2-positive metastatic breast cancer in Europe: a cohort study leveraging electronic medical records

Paul Cottu  1 , Sue Cheeseman  2 , Peter Hall  3   4 , Achim Wöckel  5 , Christian W Scholz  6 , Emilio Bria  7   8 , Armando Orlandi  7 , Nuria Ribelles  9 , Mahéva Vallet  3   4 , Nicolas Niklas  10 , Catherine Hogg  11 , Shivani Aggarwal  12 , Joana Moreira  13 , Markus Lucerna  14 , Simon M Collin  15 , Amanda Logue  16 , Gráinne H Long  15
Affiliations
Observational Study

Attrition between lines of therapy and real-world outcomes of patients with HER2-positive metastatic breast cancer in Europe: a cohort study leveraging electronic medical records

Paul Cottu et al. Breast Cancer Res Treat. 2025 Jan.

Abstract

Purpose: To characterize real-world attrition rates across first-line (1L) to third-line (3L) therapies in patients with HER2-positive (HER2 +) metastatic breast cancer (mBC) receiving routine care in seven hospital systems across Europe (France, Germany, Italy, Spain, and the UK).

Methods: This retrospective, observational, multi-country, cohort study collected electronic medical record data from women aged ≥ 18 years diagnosed with HER2 + mBC from 2017-2021. The primary endpoint was attrition rate (the proportion of patients receiving a line of therapy [LOT] with no further evidence of subsequent LOTs). Key additional endpoints included treatment patterns, real-world time to treatment discontinuation (TTD), and time to next treatment (TTNT).

Results: 29.6% (95% confidence interval [CI] 25.0-34.6) and 34.2% (95% CI 27.5-41.5) of treated patients with HER2 + mBC had no further evidence of treatment beyond 1L and second-line (2L) therapy, respectively. Attrition was primarily owing to death, move to end-of-life palliative care, loss to follow up, and "other" reasons. Treatment patterns were generally aligned with clinical guidelines. Decreases in TTD (12.1 months [95% CI 10.4-14.5] for 1L, 8.9 months [95% CI 7.3-11.9] for 2L, 6.4 months [95% CI 5.2-8.9] for 3L) and TTNT (15.4 months [95% CI 13.6-20.6] for 1L, 13.5 months [95% CI 10.8-19.4] for 2L) were observed with each subsequent LOT.

Conclusion: Results unveil a large proportion of patients who do not benefit from state-of-the-art subsequent LOT, and suggest diminishing effectiveness with each subsequent LOT.

Keywords: Attrition; Breast neoplasm; ERBB2 protein; HER2; Neoplasm metastasis; Real-world data.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare the following competing interests: N.H. has received lecture honoraria from Art Tempi, AstraZeneca, Daiichi Sankyo, Gilead, Lilly, Medscape, MSD, Novartis, Onkowissen, Pierre Fabre, Roche, Sanofi, Seagen, Viatris, and Zuelligpharma; has received consulting or advisory honoraria from Aptitude Health, Gilead, Pfizer, Sandox-Hexal, Sanofi, and Seagen; has received research funding from AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Gilead, MSD, Roche, Seagen, TRIO, and WSG; has participated on IDMC/steering committees for Lilly, Pierre Fabre, and Roche; and has ownership interest in the West German Study Group. E.C. has received lecture, consulting, or advisory honoraria from AstraZeneca, Daiichi Sankyo, Gilead, Lilly, Menarini, MSD, Novartis, Pfizer, Reveal Genomics, and Roche; has received support for attending meetings and/or travel from AstraZeneca, Pfizer, and Roche; has received research funding from Daiichi Sankyo, Pfizer, and Roche; and has participated on steering committees for AstraZeneca, Daiichi Sankyo, Gilead, Novartis, Reveal Genomics, and Roche. G.J. has received consulting honoraria from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Diaccurate, Lilly, Novartis, Pfizer, Roche, and Seagen; has received honoraria from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Lilly, Novartis, Pfizer, Roche, and Seagen; has received support for attending meetings and/or travel from Amgen, AstraZeneca Bristol Myers Squibb, Gilead, Lilly, Novartis, Pfizer, and Roche; and has received medical writing support from Amgen, AstraZeneca, Bristol Myers Squibb, Lilly, Novartis, and Roche. V.M. has received lecture honoraria from AstraZeneca, Daiichi Sankyo, Eisai, Gilead, high5 Oncology, iMED Institut, Lilly, Medac, Medscape, MSD, Novartis, Onkowissen, Pfizer, Pierre Fabre, Roche, and Seagen; has received consulting or advisory honoraria from ClinSol, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, Pierre Fabre, PINK, Roche, and Stemline; and has received research funding from AstraZeneca, Genentech, Novartis, Roche, and Seagen. N.N. has received consulting or advisory honoraria from AstraZeneca, Chugai Pharmaceutical, and Daiichi Sankyo; has received lecture honoraria from AstraZeneca, Chugai Pharmaceutical, Eisai, Daiichi Sankyo, Eli Lilly Japan, Nippon Kayaku, and Pfizer Japan; and has received research funding from Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Nippon Kayaku, and Pfizer Japan. G.V. has received research grants from Dako/Agilent Technologies, Roche/Genentech, and Ventana Medical Systems, and has received honoraria from AstraZeneca, Daiichi Sankyo, Dako/Agilent, Gilead, MSD Oncology, Pfizer, Roche, and Ventana. R.B. has held advisory roles at AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Grünenthal, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Seagen, and Stemline; has received lecture honoraria from AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Eli Lilly, Gilead, Grünenthal, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Seagen, and Stemline; and has received research support from Daiichi Sankyo, MSD, Novartis, and Roche. C.K. has received lecture honoraria from AstraZeneca, Eli Lilly, Genomic Health, Gilead, GSK, Novartis, PharmaMar, Pfizer, and Roche; has received consulting or advisory honoraria from AstraZeneca, Eli Lilly, Genomic Health, Gilead, GSK, MSD, Novartis, PharmaMar, and Roche; and has participated on steering committees for AstraZeneca. M.J.H. has received lecture honoraria from AstraZeneca. R.M.C. has received an unrestricted educational grant from Pfizer; has received research support from AstraZeneca, Daiichi Sankyo, MSD Ireland, and Pfizer; has received honoraria from AstraZeneca, Daiichi Sankyo, Gilead, Lilly, and Seagen; and has received support for attending meetings and/or travel from Gilead, Novartis, and Roche. M.G. has received support for attending meetings and/or travel from AstraZeneca, Gilead, Roche, and Pfizer, and has received honoraria from AstraZeneca, Gilead, and Pfizer. V.G. has received honoraria from AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, Menarini Stemline, MSD, Novartis, Pfizer, Olema Oncology, Pierre Fabre, and Roche; has received lecture honoraria from AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK, Menarini Stemline, Novartis, Roche, and Zentiva; and has received expert testimony honoraria from Eli Lilly. G.B. has received honoraria from Agendia, Amgen, AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Exact Science, Gilead, Helsinn Lilly, Menarini Stemline, MSD, Novartis, Pfizer, Roche, Sanofi, and Seagen, and has received a research grant from Gilead. H.W. has received lecture honoraria from Seagen; has received consulting or advisory honoraria from AstraZeneca, Augustine Therapeutics, Daiichi Sankyo, E Squared Communications LLC, Gilead, Immutep Ltd, Lilly, MediMix, Novartis, NV Hict, Pfizer, PSI CRO, Roche, and Stemline Therapeutics; has received support for attending meetings and/or travel from Daiichi Sankyo and Pfizer; has received research funding from Novartis, Roche, and Syneos Health; and has received subscription fees from Gilead. S.E.-d-R. has received honoraria from AstraZeneca, COR2ED, Daiichi Sankyo, Jazz Pharmaceuticals, Medistream, Pierre Fabre, Roche, and Seagen; has received research funding from AstraZeneca, Byondis, Daiichi Sankyo, Jazz Pharmaceuticals, MEDSIR, Roche, SOLTI, and Zymeworks; and has received support for attending meetings and/or travel from AstraZeneca, Daiichi Sankyo, Kern Pharma, Pfizer, Seagen, and SOLTI. M.P., H.B., N.K.-C., N.S., and S.V. are employees of AstraZeneca. N.K.-C. holds stocks in AstraZeneca and AbbVie. N.U.L. has received honoraria from AstraZeneca and has received research funding from AstraZeneca. The remaining authors declare no competing interests. Ethical approval: The study protocol was approved by Fondazione Policlinico Universitario Agostino Gemelli IRCCS Comitato Etico, Medizinische Ethikkommission an der Julius-Maximilians-Universität Würzburg (for University Hospital Wurzburg and Vivantes Hospital Group), HRA and Health and Care Research Wales (for Leeds Teaching Hospitals Trust and NHS Lothian, UK), CEIM Provincial de Málaga (for Unidad de Gestión Clínica Intercentros Oncology, Spain), and Comite de Revue Interne Data (for Institut Curie, France; study MR-004 compliant). Consent to participate: Not applicable. Consent to publish: Not applicable.

Figures

Fig. 1
Fig. 1
Attrition algorithm. A attrition, FU follow up, HER2 + human epidermal growth factor receptor 2-positive, LOT line of therapy, mBC metastatic breast cancer, N number of patients
Fig. 2
Fig. 2
Treatment patterns on a regimen level from 1 to 3L. 1L first line, 2L second line, 3L third line, CDK4/6i cyclin-dependent kinase 4 and 6 inhibitor, IO immunotherapy
Fig. 3
Fig. 3
Attrition rates from 1L to 2L and 2L to 3L in the overall cohort. 1L first line, 2L second line, 3L third line, CI confidence interval
Fig. 4
Fig. 4
TTNT from 1 to 3L. 1L first line, 2L second line, CI confidence interval, LOT line of therapy, TTNT time to next treatment
See this image and copyright information in PMC

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