PACE: A randomized phase II study of fulvestrant, palbociclib, and avelumab after progression on cyclin-dependent kinase 4/6 inhibitor and aromatase inhibitor for hormone receptor-positive/human epidermal growth factor receptor-negative metastatic breast cancer

Authors

Erica L. Mayer, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Yue Ren, Department of Data Science, Dana-Farber Cancer Institute, Boston, MA.
Nikhil Wagle, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Reshma Mahtani, Department of Medical Oncology, Miami Cancer Institute, Miami, FL.
Cynthia Ma, Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO.
Angela DeMichele, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
Massimo Cristofanilli, Department of Medical Oncology, Weill Cornell Medicine, New York, NY.
Jane Meisel, Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA.
Kathy D. Miller, Hematology/Oncology Division, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.
Yara Abdou, Department of Medicine, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC.
Elizabeth C. Riley, Department of Medicine, Brown Cancer Center, University of Louisville Health, Louisville, KY.
Rubina Qamar, Advocate Health - MidwestFollow
Priyanka Sharma, Department of Medical Oncology, University of Kansas Medical Center, Westwood, KS.
Sonya Reid, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN.
Natalie Sinclair, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Meredith Faggen, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Caroline C. Block, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Naomi Ko, Department of Medical Oncology, Boston Medical Center, Boston, MA.
Ann H. Partridge, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Wendy Y. Chen, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Michelle DeMeo, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Victoria Attaya, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Amanda Okpoebo, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Jillian Alberti, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Yuan Liu, Pfizer, La Jolla, CA.
Eric Gauthier, Pfizer, La Jolla, CA.
Harold J. Burstein, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Meredith M. Regan, Harvard Medical School, Boston, MA.
Sara M. Tolaney, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.

Abstract

Purpose: Cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6is) are an important component of treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), but it is not known if patients might derive benefit from continuation of CDK4/6i with endocrine therapy beyond initial tumor progression or if the addition of checkpoint inhibitor therapy has value in this setting.

Methods: The randomized multicenter phase II PACE trial enrolled patients with hormone receptor-positive/HER2- MBC whose disease had progressed on previous CDK4/6i and aromatase inhibitor (AI) therapy. Patients were randomly assigned 1:2:1 to receive fulvestrant (F), fulvestrant plus palbociclib (F + P), or fulvestrant plus palbociclib and avelumab (F + P + A). The primary end point was investigator-assessed progression-free survival (PFS) in patients treated with F versus F + P.

Results: Overall, 220 patients were randomly assigned between September 2017 and February 2022. The median age was 57 years (range, 25-83 years). Most patients were postmenopausal (80.9%), and 40% were originally diagnosed with de novo MBC. Palbociclib was the most common previous CDK4/6i (90.9%). The median PFS was 4.8 months on F and 4.6 months on F + P (hazard ratio [HR], 1.11 [90% CI, 0.79 to 1.55]; P = .62). The median PFS on F + P + A was 8.1 months (HR v F, 0.75 [90% CI, 0.50 to 1.12]; P = .23). The difference in PFS with F + P and F + P + A versus F was greater among patients with baseline ESR1 and PIK3CA alterations.

Conclusion: The addition of palbociclib to fulvestrant did not improve PFS versus fulvestrant alone among patients with hormone receptor-positive/HER2- MBC whose disease had progressed on a previous CDK4/6i plus AI. The increased PFS seen with the addition of avelumab warrants further investigation in this patient population.

Type

Article

PubMed ID

38513188


 

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