Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial

Sara M Tolaney; Paolo Tarantino; Noah Graham; Nabihah Tayob; Laia Parè; Guillermo Villacampa; Chau T Dang; Denise A Yardley; Beverly Moy; P Kelly Marcom; Kathy S Albain; Hope S Rugo; Matthew J Ellis; Iuliana Shapira; Antonio C Wolff; Lisa A Carey; Romualdo Barroso-Sousa; Patricia Villagrasa; Michelle DeMeo; Molly DiLullo; Jorge Gomez Tejeda Zanudo; Jakob Weiss; Nikhil Wagle; Ann H Partridge; Adrienne G Waks; Clifford A Hudis; Ian E Krop; Harold J Burstein; Aleix Prat; Eric P Winer

doi:10.1016/S1470-2045(23)00051-7

Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial

Lancet Oncol. 2023 Mar;24(3):273-285. doi: 10.1016/S1470-2045(23)00051-7.

Authors

Sara M Tolaney¹, Paolo Tarantino², Noah Graham³, Nabihah Tayob³, Laia Parè⁴, Guillermo Villacampa⁴, Chau T Dang⁵, Denise A Yardley⁶, Beverly Moy⁷, P Kelly Marcom⁸, Kathy S Albain⁹, Hope S Rugo¹⁰, Matthew J Ellis¹¹, Iuliana Shapira¹², Antonio C Wolff¹³, Lisa A Carey¹⁴, Romualdo Barroso-Sousa¹⁵, Patricia Villagrasa⁴, Michelle DeMeo¹⁶, Molly DiLullo¹⁶, Jorge Gomez Tejeda Zanudo¹⁷, Jakob Weiss¹⁸, Nikhil Wagle¹⁹, Ann H Partridge²⁰, Adrienne G Waks²⁰, Clifford A Hudis²¹, Ian E Krop²², Harold J Burstein²⁰, Aleix Prat²³, Eric P Winer²²

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: sara_tolaney@dfci.harvard.edu.
² Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; European Institute of Oncology IRCCS, Milan, Italy.
³ Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA.
⁴ Reveal Genomics, Barcelona, Spain.
⁵ Solid Tumor Division, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁶ Department of Medical Oncology, Sarah Cannon Cancer Center, Nashville, TN, USA.
⁷ Department of Hematology-Oncology, Massachusetts General Hospital, Boston, MA, USA.
⁸ Department of Medicine, Division of Medical Oncology, Duke Cancer Institute, Durham, NC, USA.
⁹ Department of Medicine, Division of Hematology-Oncology, Loyola University Medical Center, Maywood, IL, USA.
¹⁰ Department of Medicine, Division of Oncology, University of California, San Francisco, CA, USA.
¹¹ Baylor Clinic Lester and Sue Smith Breast Center, Houston, TX, USA.
¹² Regional Cancer Care Associates, New Hyde Park, New York, NY, USA.
¹³ Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
¹⁴ Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
¹⁵ DASA Oncology, Brasilia Hospital, Diagnósticos da América SA (DASA), Brasília, Brazil.
¹⁶ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
¹⁷ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Boston, MA, USA.
¹⁸ Broad Institute of MIT and Harvard, Boston, MA, USA.
¹⁹ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Boston, MA, USA.
²⁰ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
²¹ Solid Tumor Division, Memorial Sloan Kettering Cancer Center, New York, NY, USA; American Society of Clinical Oncology, Alexandria, VA, USA.
²² Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Yale Cancer Center, New Haven, CT, USA.
²³ Reveal Genomics, Barcelona, Spain; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain.

PMID: 36858723
DOI: 10.1016/S1470-2045(23)00051-7

Abstract

Background: We aimed to report on long-term outcomes of patients with small, node-negative, HER2-positive breast cancer treated with adjuvant paclitaxel and trastuzumab and to establish potential biomarkers to predict prognosis.

Methods: In this open-label, single-arm, phase 2 study, patients aged 18 years or older, with small (≤3 cm), node-negative, HER2-positive breast cancer, and an Eastern Cooperative Oncology Group performance status of 0-1, were recruited from 16 institutions in 13 cities in the USA. Eligible patients were given intravenous paclitaxel (80 mg/m²) with intravenous trastuzumab (loading dose of 4 mg/kg, subsequent doses 2 mg/kg) weekly for 12 weeks, followed by trastuzumab (weekly at 2 mg/kg or once every 3 weeks at 6 mg/kg) for 40 weeks to complete a full year of trastuzumab. The primary endpoint was 3-year invasive disease-free survival. Here, we report 10-year survival outcomes, assessed in all participants who received protocol-defined treatment, with exploratory analyses using the HER2DX genomic tool. This study is registered on ClinicalTrials.gov, NCT00542451, and is closed to accrual.

Findings: Between Oct 29, 2007, and Sept 3, 2010, 410 patients were enrolled and 406 were given adjuvant paclitaxel and trastuzumab and included in the analysis. Mean age at enrolment was 55 years (SD 10·5), 405 (99·8%) of 406 patients were female and one (0·2%) was male, 350 (86·2%) were White, 28 (6·9%) were Black or African American, and 272 (67·0%) had hormone receptor-positive disease. After a median follow-up of 10·8 years (IQR 7·1-11·4), among 406 patients included in the analysis population, we observed 31 invasive disease-free survival events, of which six (19·4%) were locoregional ipsilateral recurrences, nine (29·0%) were new contralateral breast cancers, six (19·4%) were distant recurrences, and ten (32·3%) were all-cause deaths. 10-year invasive disease-free survival was 91·3% (95% CI 88·3-94·4), 10-year recurrence-free interval was 96·3% (95% CI 94·3-98·3), 10-year overall survival was 94·3% (95% CI 91·8-96·8), and 10-year breast cancer-specific survival was 98·8% (95% CI 97·6-100). HER2DX risk score as a continuous variable was significantly associated with invasive disease-free survival (hazard ratio [HR] per 10-unit increment 1·24 [95% CI 1·00-1·52]; p=0·047) and recurrence-free interval (1·45 [1·09-1·93]; p=0·011).

Interpretation: Adjuvant paclitaxel and trastuzumab is a reasonable treatment standard for patients with small, node-negative, HER2-positive breast cancer. The HER2DX genomic tool might help to refine the prognosis for this population.

Funding: Genentech.

Publication types

Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

Breast
Breast Neoplasms*
Female
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
Paclitaxel
Trastuzumab

Substances

Trastuzumab
Paclitaxel

Associated data

ClinicalTrials.gov/NCT00542451