'ADVANCE' (a pilot trial) ADjuVANt chemotherapy in the elderly: Developing and evaluating lower-toxicity chemotherapy options for older patients with breast cancer

Rachel A Freedman; Tianyu Li; Mina S Sedrak; Judith O Hopkins; Nabihah Tayob; Meredith G Faggen; Natalie F Sinclair; Wendy Y Chen; Heather A Parsons; Erica L Mayer; Paulina B Lange; Ameer S Basta; Adriana Perilla-Glen; Ruth I Lederman; Andrew Wong; Abhay Tiwari; Sandra S McAllister; Elizabeth A Mittendorf; Peter G Miller; Christopher J Gibson; Harold J Burstein

doi:10.1016/j.jgo.2022.09.006

'ADVANCE' (a pilot trial) ADjuVANt chemotherapy in the elderly: Developing and evaluating lower-toxicity chemotherapy options for older patients with breast cancer

J Geriatr Oncol. 2023 Jan;14(1):101377. doi: 10.1016/j.jgo.2022.09.006. Epub 2022 Sep 23.

Authors

Rachel A Freedman¹, Tianyu Li², Mina S Sedrak³, Judith O Hopkins⁴, Nabihah Tayob⁵, Meredith G Faggen⁶, Natalie F Sinclair⁷, Wendy Y Chen⁸, Heather A Parsons⁸, Erica L Mayer⁸, Paulina B Lange⁹, Ameer S Basta⁹, Adriana Perilla-Glen⁹, Ruth I Lederman⁹, Andrew Wong³, Abhay Tiwari³, Sandra S McAllister¹⁰, Elizabeth A Mittendorf¹¹, Peter G Miller¹², Christopher J Gibson¹³, Harold J Burstein⁸

Affiliations

¹ 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: rafreedman@partners.org.
² Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.
³ Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
⁴ Novant Health Cancer Institute / SCOR NCORP, Winston Salem, NC, USA.
⁵ Harvard Medical School, Boston, MA, USA; Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.
⁶ Dana-Farber Brigham Cancer Center at South Shore Hospital, South Weymouth, MA, USA.
⁷ Dana-Farber Brigham Cancer Center at Milford Regional Medical Center, Milford, MA, USA.
⁸ 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.
⁹ Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
¹⁰ Harvard Medical School, Boston, MA, USA; Hematology Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
¹¹ Breast Oncology Program, Dana-Farber Brigham Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
¹² Harvard Medical School, Boston, MA, USA; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
¹³ Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.

Abstract

Introduction: Older adults with breast cancer receiving neo/adjuvant chemotherapy are at high risk for poor outcomes and are underrepresented in clinical trials. The ADVANCE (ADjuVANt Chemotherapy in the Elderly) trial evaluated the feasibility of two neo/adjuvant chemotherapy regimens in parallel-enrolling cohorts of older patients with human epidermal growth factor receptor 2-negative breast cancer: cohort 1-triple-negative; cohort 2-hormone receptor-positive.

Materials and methods: Adults age ≥ 70 years with stage I-III breast cancer warranting neo/adjuvant chemotherapy were enrolled. Cohort 1 received weekly carboplatin (area under the curve 2) and weekly paclitaxel 80 mg/m² for twelve weeks; cohort 2 received weekly paclitaxel 80 mg/m² plus every-three-weekly cyclophosphamide 600 mg/m² over twelve weeks. The primary study endpoint was feasibility, defined as ≥80% of patients receiving ≥80% of intended weeks/doses of therapy. All dose modifications were applied per clinician discretion.

Results: Forty women (n = 20 per cohort) were enrolled from March 25, 2019 through August 3, 2020 from three centers; 45% and 35% of patients in cohorts 1 and 2 were age > 75, respectively. Neither cohort achieved targeted thresholds for feasibility. In cohort 1, eight (40.0%) met feasibility (95% confidence interval [CI] = 19.1-63.9%), while ten (50.0%) met feasibility in cohort 2 (95% CI = 27.2-72.8). Neutropenia was the most common grade 3-4 toxicity (cohort 1-65%, cohort 2-55%). In cohort 1, 80% and 85% required ≥1 dose holds of carboplatin and/or paclitaxel, respectively. In cohort 2, 10% required dose hold(s) for cyclophosphamide and/or 65% for paclitaxel.

Discussion: In this pragmatic pilot examining chemotherapy regimens in older adults with breast cancer, neither regimen met target goals for feasibility. Developing efficacious and tolerable regimens for older patients with breast cancer who need chemotherapy remains an important goal.

Clinicaltrials: gov Identifier: NCT03858322.

Keywords: Breast cancer; Carboplatin; Chemotherapy; Cyclophosphamide; Older adults; Paclitaxel.

MeSH terms

Aged
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Breast Neoplasms* / drug therapy
Carboplatin
Chemotherapy, Adjuvant
Cyclophosphamide
Female
Humans
Paclitaxel
Pilot Projects

'ADVANCE' (a pilot trial) ADjuVANt chemotherapy in the elderly: Developing and evaluating lower-toxicity chemotherapy options for older patients with breast cancer

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