Matteo Lambertini MD PhD; San Antonio Breast Cancer Symposium: ALTTO Trial Shows Adjuvant Aromatase Inhibitors Outperform Tamoxifen in Patients with ER-Positive, HER2-Positive Early Breast Cancer  

Matteo Lambertini MD PhD; San Antonio Breast Cancer Symposium: ALTTO Trial Shows Adjuvant Aromatase Inhibitors Outperform Tamoxifen in Patients with ER-Positive, HER2-Positive Early Breast Cancer

An interview with:

Matteo Lambertini MD PhD, Assistant Professor, University of Genoa, Consultant in Medical Oncology, San Martino IST Hospital, Genoa, Italy.

SAN ANTONIO, USA­—Patients with hormone receptor positive HER2-positive early breast cancer had superior outcomes when treated with aromatase inhibitor adjuvant therapy than similar patients treated with adjuvant tamoxifen or other selective estrogen receptor modulators (SERMs). This is the headline finding from a long-term analysis of the large international ALTTO trial reported at the 2025 San Antonio Breast Cancer Symposium by Matteo Lambertini MD PhD, Assistant Professor at the University of Genoa, and Consultant in Medical Oncology, San Martino IST Hospital in Genoa, Italy. After his talk at the conference he discussed the findings with the Audio Journal of Oncology’s Peter Goodwin:

AUDIO JOURNAL OF ONCOLOGY: Matteo Lambertini MD PhD

IN: [GOODWIN] “Matteo Lambertini I am with you here at the San …….. OUT: ……for the Audio Journal of Oncology, I’m Peter Goodwin. 7:05 secs

CONFERENCE DETAILS:

2025 San Antonio Breast Cancer Symposium, San Antonio, Texas USA

ORAL SESSION: GS1-03

“Adjuvant aromatase inhibitor or tamoxifen in patients with hormone receptor-positive/HER2-positive early breast cancer: An exploratory analysis from the ALTTO (BIG 2-06) trial”

SPEAKER:

Matteo Lambertini, University of Genova – IRCCS Ospedale Policlinico San Martino, Genoa, Italy

AUTHORS:

1. Lambertini1, F. Samy2, E. Agostinetto3, L. Arecco4, P. Freire5, A. Sonnenblick6, G. Arpino7, L. Del Mastro8, A. Choudhury9, N. Harbeck10, I. Vaz-Luis11, V. Kaklamani12, A. Wolff13, A. Partridge14, S. Loi15, S. Fielding16, M. Piccart17, S. Di Cosimo18, E. de Azambuja17;

INSTITUTIONS:

1Medical Oncology, University of Genova - IRCCS Ospedale Policlinico San Martino, Genoa, ITALY, 2Statistics, Frontier Science Scotland, Kingussie, UNITED KINGDOM, 3Oncology, Institut Jules Bordet, Hôpital Universitaire de Bruxelles (H.U.B) and Université Libre de Bruxelles (U.L.B.), Brussels, BELGIUM, 4Oncology, Department of Oncology, Institut Jules Bordet, Hôpital Universitaire de Bruxelles (H.U.B) and Université Libre de Bruxelles (U.L.B.), Brussels, BELGIUM, 5Medical Oncology, Oncologia D’Or Hospital de Câncer de Pernambuco, Recife, BRAZIL, 6Medical Oncology, The Oncology Division, Tel Aviv Sourasky Medical Center, Grey Faculty of Medicine, Tel Aviv University, Tel Aviv, ISRAEL, 7Medical Oncology, Università di Napoli Federico II, Naples, ITALY, 8Medical Oncology, University of Genova - IRCCS Ospedale Policlinico San Martino, Genova, ITALY, 9-, Novartis, Hyderabad, INDIA, 10Oncology, Dept. OB&GYN and CCC Munich, LMU University Hospital, Munich, GERMANY, 11Medical Oncology, Institut Gustave Roussy, Villejuif, FRANCE, 12Medical Oncology, UTH San Antonio, San Antonio, TX, 13Medical Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 14Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 15Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, AUSTRALIA, 16Stat, Frontier Science Scotland, Kingussie, UNITED KINGDOM, 17Medical Oncology, Department of Oncology, Institut Jules Bordet, Hôpital Universitaire de Bruxelles (H.U.B) and Université Libre de Bruxelles (U.L.B.), Brussels, BELGIUM, 18Medical Oncology, Istituto Nazionale dei Tumori (INT), Milano, ITALY.

DISCLOSURES:

1. Lambertini: Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, Menarini, Nordic Pharma , Roche, Lilly, Novartis, Pfizer, AstraZeneca, Takeda, Ipsen, Sandoz, Libbs, Daiichi Sankyo, Gilead, Menarini, Gilead, Daiichi Sankyo, Roche, Gilead (to the institution).

BACKGROUND:

The optimal adjuvant endocrine therapy (ET) for patients (pts) with hormone receptor-positive (HR+)/HER2-positive (HER2+) early breast cancer (EBC) remains controversial. The present analysis investigated the efficacy of different types of ET in pts with centrally tested HR+/HER2+ EBC treated with modern chemotherapy (CT) and trastuzumab (T)-based regimens at 10-year follow-up.

Patients and methods: ALTTO (BIG 2-06) is an international phase 3 trial in pts with HER2+ EBC randomized to 4 adjuvant anti-HER2 treatments with CT: T alone, lapatinib (L) alone, their sequence (T->L) or their combination (T+L). Pts in the L alone arm, pts with HR-/HER2+ disease and pts with HR+ tumours who did not start adjuvant ET were excluded from the analysis. HER2 and HR status were centrally tested for all pts. Disease-free survival (DFS), time to distant recurrence (TTDR) and overall survival (OS) were compared between pts who received a selective estrogen receptor modulator (SERM) vs. those who received an aromatase inhibitor (AI). To avoid the risk of immortal time bias, pts with HR+/HER2+ disease who switched from one ET to another during the follow-up were excluded. A pre-planned subgroup analysis according to menopausal status at baseline was performed. Among premenopausal women, a comparison was made between SERM alone, SERM + ovarian function suppression (OFS) and AI±OFS (depending on post-CT menopausal status). Multivariable Cox proportional hazards regression models were used to model survival outcomes with adjuvant ET as the predictor. Other covariates in the model were CT timing (concurrent/sequential), tumour grade (G1/2, G3, GX), age (continuous) and tumour size (T, continuous) and a strata variable of axillary lymph node (N0, N1-3, N>=4 nodes, N/A). SERM were used as the reference category for adjusted hazard ratios (aHR).

RESULTS:

This analysis included 2,651 pts with HR+/HER2+ of whom 1,518 (57.3%) received SERM (99.5% tamoxifen) and 1,133 (42.7%) AI. Among 1,259 premenopausal pts, 903 (71.7%) received SERM alone, 238 (18.9%) SERM+OFS and 118 (9.4%) AI±OFS. Median follow-up was 9.9 years (IQR 7.0-10.0 years). Overall, 10-year DFS was 80.1% and 76.5% in the AI and SERM groups, respectively (aHR 0.65; 95% CI 0.52-0.82). Compared to pts treated with SERM, those who received AI had fewer local (0.9% vs. 2.4%) and distant (9.3% vs. 12.1%) recurrences. In subgroup analyses, AI was superior to SERM irrespective of pts (age, menopausal status, body mass index), tumor (T, N, G, HR+ levels, HER2 FISH ratio) and treatment (anti-HER2 arm, CT type and timing) characteristics. In the AI and SERM groups, 10-year TTDR was 85.7% and 83.1% (aHR 0.65; 95% CI 0.50-0.85), and 10-year OS was 88.9% and 89.1% (aHR 0.73; 95% CI 0.53-1.00), respectively. Among premenopausal pts only, 10-year DFS was 90.0%, 77.3% and 77.6% with AI±OFS, SERM+OFS and SERM, respectively (AI±OFS vs. SERM: aHR 0.44; 95% CI 0.23-0.85; SERM+OFS vs. SERM: aHR 0.87; 95% CI 0.61-1.23). In the AI±OFS, SERM+OFS and SERM groups, 10-year TTDR was 92.8%, 82.9% and 85.1% (AI±OFS vs. SERM: aHR 0.57; 95% CI 0.27-1.18; SERM+OFS vs. SERM: aHR 0.94; 95% CI 0.62-1.41), and 10-year OS was 95.6%, 88.7% and 91.3% (AI±OFS vs. SERM: aHR 0.68; 95% CI 0.27-1.73; SERM+OFS vs. SERM: aHR 0.98; 95% CI 0.58-1.66), respectively.

CONCLUSIONS:

In this large 10-year follow-up analysis of pts with centrally tested HR+/HER2+ EBC treated with modern CT+anti-HER2-based therapy in the ALTTO trial, the use of AI was associated with significantly improved DFS and TTDR without differences in OS. The DFS benefit of AI was observed in both premenopausal and postmenopausal pts. These data may help optimizing adjuvant ET choices in pts with HR+/HER2+ EBC and shed light on the need of designing ad hoc clinical trials in this setting.

AJO January 9, 2025: Matteo Lambertini, San Antonio BC Symposium