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

Author(s): Erica L. Mayer, MD, MPH1,2, Yue Ren, MS3, Nikhil Wagle, MD1,2, Reshma Mahtani, DO4, Cynthia Ma, MD, PhD5, Angela DeMichele, MD, MSCE6, Massimo Cristofanilli, MD7, Jane Meisel, MD8, Kathy D. Miller, MD9, Yara Abdou, MD10, Elizabeth C. Riley, MD11, Rubina Qamar, MD12, Priyanka Sharma, MD13, Sonya Reid, MD, MPH14, Natalie Sinclair, MD1, Meredith Faggen, MD1, Caroline C. Block, MD1,2, Naomi Ko, MD15, Ann H. Partridge, MD, MPH1,2, Wendy Y. Chen, MD, MPH1,2, Michelle DeMeo, BS1, Victoria Attaya, BA1, Amanda Okpoebo, MS1, Jillian Alberti, MS1, Yuan Liu, PhD16, Eric Gauthier, PhD, PharmD16, Harold J. Burstein, MD, PhD1,2, Meredith M. Regan, ScD2,3, Sara M. Tolaney, MD, MPH1,2
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

Findings from the PACE study show that the addition of Palbociclib to Fulvestrant was not better than Fulvestrant alone, and the addition of Avelumab to Fulvestrant improved and nearly doubled the PFS. This is compelling and should be studied further for our patients with HR+ HER2- MBC.


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.


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.


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.


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.

Author Affiliations

1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 2Harvard Medical School, Boston, MA, 3Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, 4Department of Medical Oncology, Miami Cancer Institute, Miami, FL, 5Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO, 6Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, 7Department of Medical Oncology, Weill Cornell Medicine, New York, NY, 8Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 9Hematology/Oncology Division, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 10Department of Medicine, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, 11Department of Medicine, Brown Cancer Center, University of Louisville Health, Louisville, KY, 12Aurora Cancer Care, Milwaukee, WI, 13Department of Medical Oncology, University of Kansas Medical Center, Westwood, KS, 14Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 15Department of Medical Oncology, Boston Medical Center, Boston, MA, 16Pfizer, La Jolla, CA

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