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Randomized Controlled Trial
. 2022 Nov;127(10):1799-1807.
doi: 10.1038/s41416-022-01963-8. Epub 2022 Sep 1.

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

Guilherme Nader-Marta  1 , Véronique Debien  2 , Daniel Eiger  2 , Zoi Tsourti  3 , Rafael Caparica  2 , Marie Kassapian  3 , Sylvia Napoleone  2 , Susanne Hultsch  4 , Larissa Korde  5 , Yingbo Wang  6 , Saranya Chumsri  7 , Kathleen I Pritchard  8   9 , Michael Untch  10 , Meritxell Bellet-Ezquerra  11 , Daniela Dornelles Rosa  12 , Alvaro Moreno-Aspitia  7 , Martine Piccart  2 , Urania Dafni  13 , Evandro de Azambuja  2
Affiliations
Randomized Controlled Trial

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

Guilherme Nader-Marta et al. Br J Cancer. 2022 Nov.

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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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1. Consort diagram.
Patient allocation between arms in the original ALTTO study and in the small tumours sub-analysis.
Fig. 2
Fig. 2
Disease-free survival by treatment arm in patients with small tumours enrolled in ALTTO.
Fig. 3
Fig. 3
Overall survival by treatment arm in patients with small tumours enrolled in ALTTO.
Fig. 4
Fig. 4
Time-to-distant recurrence by treatment arm in patients with small tumours enrolled in ALTTO.
See this image and copyright information in PMC

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