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Clinical Studies

Outcomes of patients with small and node-negative HER2-positive early breast cancer treated with adjuvant chemotherapy and anti-HER2 therapy—a sub-analysis of the ALTTO study

British Journal of Cancer volume 127, pages 1799–1807 (2022)Cite this article

Subjects

Abstract

Background

Patients with small node-negative HER2-positive breast cancer are commonly treated with paclitaxel and 1 year of adjuvant trastuzumab. We performed a sub-analysis of the ALTTO trial to explore the long-term outcomes of patients with small node-negative tumours.

Methods

The ALTTO trial randomised 8381 patients with early HER2-positive BC treated with adjuvant chemotherapy (anthracycline/taxane- or taxane/carboplatin-based), to trastuzumab (T), lapatinib (L), their sequence (T → L) or their combination (L + T). Patients with tumours ≤3 cm and node-negative were included in this sub-analysis.

Results

A total of 2821 patients were analysed (median follow-up of 7 years). The median age was 52 years, and most patients had tumours ≤2 cm (64.3%). The 7-year disease-free survival (DFS) was 88.1% (95% CI: 86.7–89.3%). DFS was similar for arms T, T + L and T⟶L and significantly lower for arm L (stratified log-rank P = 0.031). The 7-year overall survival rate was 95.9% (95% CI: [95.0–96.6%) and the 7-year time-to-distant recurrence was 93.4% (95% CI: 92.3–94.4%).

Conclusion

With most patients treated with anthracycline-based regimens, ALTTO shows that patients with small tumours treated with trastuzumab and concomitant chemotherapy have excellent long-term outcomes, similar to those of the APT trial.

Trial registration

Clinicaltrials.gov identifier NCT00490139.

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Data availability

Not applicable.

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Acknowledgements

We acknowledge the ALTTO staff of Clinical Trial Support Unit (CTSU) at Institut Jules Bordet in Brussels (Belgium) for clinical record management.

Funding

The ALTTO trial received financial support from GlaxoSmithKline (until January 2015), Novartis Pharma AG (as of January 2015), and the National Cancer Institute of the National Institutes of Health (NCI-NIH; Grant No. U10CA180821 and U10CA180882 to the Alliance for Clinical Trials in Oncology and Grant No. CA025224 to the legacy North Central Cancer Treatment Group, and Grant No. CA180863). The present analysis did not receive additional funding. The funders and sponsors had no role in the design or conduct of the study, in the collection, analysis or interpretation of the data, and in the preparation, review or approval of this paper.

Author information

Authors and Affiliations

  1. Institut Jules Bordet, and l’Université Libre de Bruxelles (U.L.B.), Brussels, Belgium

    Guilherme Nader-Marta, Véronique Debien, Daniel Eiger, Rafael Caparica, Sylvia Napoleone, Martine Piccart & Evandro de Azambuja

  2. Frontier Science Foundation Hellas, Athens, Greece

    Zoi Tsourti & Marie Kassapian

  3. Breast International Group (BIG), Brussels, Belgium

    Susanne Hultsch

  4. Breast Cancer Therapeutics, CTEP, NCI, Seattle, WA, USA

    Larissa Korde

  5. Oncology, Novartis Pharmaceuticals Corporation, Basel, Switzerland

    Yingbo Wang

  6. Jacoby Center for Breast Health; Mayo Clinic, Jacksonville, FL, USA

    Saranya Chumsri & Alvaro Moreno-Aspitia

  7. Medical Oncology/Hematology, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada

    Kathleen I. Pritchard

  8. Canadian Cancer Trials Group (CCTG), Kingston, ON, Canada

    Kathleen I. Pritchard

  9. Clinic for Gynecology, Gynecologic Oncology and Obstetrics, Helios Klinikum Berlin Buch, Berlin, Germany

    Michael Untch

  10. Oncology Department, Vall d’Hebron Institute of Oncology (VHIO) - Cellex Center, Barcelona, Spain

    Meritxell Bellet-Ezquerra

  11. Oncology Unit, Hospital Moinhos de Vento, Porto Alegre, RS, Brazil

    Daniela Dornelles Rosa

  12. Public Health Department, University of Athens, Athens, Greece

    Urania Dafni

Authors
  1. Guilherme Nader-Marta
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  2. Véronique Debien
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  4. Zoi Tsourti
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  7. Sylvia Napoleone
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  8. Susanne Hultsch
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  9. Larissa Korde
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  10. Yingbo Wang
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  13. Michael Untch
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  14. Meritxell Bellet-Ezquerra
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  15. Daniela Dornelles Rosa
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  16. Alvaro Moreno-Aspitia
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  17. Martine Piccart
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  19. Evandro de Azambuja
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Contributions

GN-M: conceptualisation, methodology and writing—original draft. VD: writing—original draft. DE: conceptualisation, methodology and writing—original draft. ZT: methodology, formal analysis and writing—original draft. RC: conceptualisation, methodology and writing—original draft. MK: methodology, formal analysis and writing—original draft. SN: investigation and data curation. SH: investigation and project administration. LK: investigation and project administration. YW: investigation and funding acquisition. SC: methodology and supervision. KP: conceptualisation and methodology. MU: methodology and supervision. MB-E: investigation and writing—review and editing. DDR: investigation, data curation and writing—review and editing. AM-A: conceptualisation, methodology, supervision and writing—review and editing. MP: conceptualisation, methodology, supervision, writing—review and editing. UD: methodology, formal analysis and writing—original draft. EdA: conceptualisation, methodology, supervision and writing—review and editing.

Corresponding author

Correspondence to Guilherme Nader-Marta.

Ethics declarations

Competing interests

GN-M: travel grants for meetings from Roche and Bayer, outside the submitted work. DE: employed by Roche, owner of Roche’s stocks. RC: Novartis employee, owner of Novartis’ stocks. YW: Employed by Novartis and holds Novartis stock. SC: research funding to her institution from Merck & Co., Pfizer, Salix Pharmaceuticals, and Rebiotix Inc. She receives consulting fees to her institution from AstraZeneca, Daiichi-Sankyo, Immunomedics, Biotheranostics, Novartis, Athenex, Syndax, Puma Biotechnology, Eisai, and Seagen. KP: consultant/advisory role: Pfizer, Roche, Amgen, Novartis, Eisai, Genomic Health Inc., Myriad Genetic Laboratories, Gilead Sciences. Royalties: UpToDate. MU: consultations and lectures (all fees to the employer/institution): Abbvie; Amgen; AstraZeneca; BMS; Daiji Sankyo; Gilead; GSK; Lilly; MSD Merck; Myriad Genetics; Novartis; Pierre Fabre; Pfizer, Roche; Sanofi Aventis; Saegen. MB-E: honoraria and/or advisory board from Pfizer, Novartis and Lilly. Travel grants from Pfizer. DDR: honoraria and/or advisory board from Roche, Novartis, Lilly, Pfizer, Daiichi-Sankyo, Zodiac, Libbs, United Medical and AstraZeneca; travel grants from Roche and Novartis; research grant to my institution from Novartis. AM-A: Institutional research funds from Genentech, GSK/Novartis and Sermonix. MP: board member (Scientific Board) from Oncolytics, consultant (honoraria) from AstraZeneca, Camel-IDS/Precirix, Gilead, Immunomedics, Lilly, Menarini, MSD, Novartis, Odonate, Pfizer, Roche-Genentech, Seattle Genetics, Immutep, Seagen, NBE Therapeutics, and Frame Therapeutics. Institutional research grants from AstraZeneca, Immunomedics, Lilly, Menarini, MSD, Novartis, Pfizer, Radius, Roche-Genentech, Servier, and Synthon (all outside the submitted work). UD: Honorarium as Member of the Tumour Agnostic Evidence Generation working Group of Roche, outside the submitted work. EdA: honoraria and/or advisory board from Roche/GNE, Novartis, Seattle Genetics, Zodiac, Libbs and Pierre Fabre Travel grants from Roche/GNE and GSK/Novartis Research grant to my institution from Roche/GNE, AstraZeneca, GSK/Novartis and Servier. The remaining authors declare no competing interest.

Ethics approval and consent to participate

All patients gave written informed consent, and institutional review board/institutional ethics committee approval to conduct the study was mandatory for all participating centres. The study was performed in accordance with the Declaration of Helsinki.

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Nader-Marta, G., Debien, V., Eiger, D. et al. Outcomes of patients with small and node-negative HER2-positive early breast cancer treated with adjuvant chemotherapy and anti-HER2 therapy—a sub-analysis of the ALTTO study. Br J Cancer 127, 1799–1807 (2022). https://doi.org/10.1038/s41416-022-01963-8

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