TY - JOUR
T1 - 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
AU - Mayer, Erica L
AU - Ren, Yue
AU - Wagle, Nikhil
AU - Mahtani, Reshma
AU - Ma, Cynthia
AU - DeMichele, Angela
AU - Cristofanilli, Massimo
AU - Meisel, Jane
AU - Miller, Kathy D
AU - Abdou, Yara
AU - Riley, Elizabeth C
AU - Qamar, Rubina
AU - Sharma, Priyanka
AU - Reid, Sonya
AU - Sinclair, Natalie
AU - Faggen, Meredith
AU - Block, Caroline C
AU - Ko, Naomi
AU - Partridge, Ann H
AU - Chen, Wendy Y
AU - DeMeo, Michelle
AU - Attaya, Victoria
AU - Okpoebo, Amanda
AU - Alberti, Jillian
AU - Liu, Yuan
AU - Gauthier, Eric
AU - Burstein, Harold J
AU - Regan, Meredith M
AU - Tolaney, Sara M
AU - Complex General Surgical Oncology Faculty, Aurora
N1 - Mayer EL, Ren Y, Wagle N, et al. 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. J Clin Oncol. 2024;42(17):2050-2060. doi:10.1200/JCO.23.01940
PY - 2024/6/10
Y1 - 2024/6/10
N2 - 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.
AB - 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.
KW - Cyclin-dependent kinase
KW - CDK
KW - hormone receptor-positive
KW - human epidermal growth factor receptor 2-negative
KW - HER2-
KW - metastatic breast cancer
KW - MBC
UR - https://institutionalrepository.aah.org/auroragme/420
UR - https://libkey.io/libraries/1712/10.1200/JCO.23.01940
U2 - 10.1200/JCO.23.01940
DO - 10.1200/JCO.23.01940
M3 - Article
C2 - 38513188
VL - 42
SP - 2050
EP - 2060
JO - Aurora GME
JF - Aurora GME
IS - 17
ER -