Continuing CDK4/6 inhibitor therapy and switching endocrine therapy (ET) after disease progression does not improve progression-free survival (PFS), when compared with switching ET alone, in patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, new research suggests. 

The phase 2 PACE trial showed that patients who received palbociclib and fulvestrant after progression on prior CDK4/6 inhibitor therapy and ET had similar PFS as patients who switched to fulvestrant and did not receive palbociclib. Adding avelumab to treatment with palbociclib and fulvestrant resulted in a numeric improvement in PFS, but statistical significance was not reached. 

These results were presented at the San Antonio Breast Cancer Symposium 2022 by Erica L. Mayer, MD, of Dana-Farber Cancer Institute in Boston.

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The PACE trial ( Identifier: NCT03147287) included 220 patients with HR-positive, HER2-negative metastatic breast cancer who had no prior treatment with fulvestrant. The median age at baseline was 57 years (range 25-83), 99% of patients were women, and 80.9% were postmenopausal. Most patients (72.7%) had endocrine-sensitive disease, 90.9% had previously received palbociclib, and 75.9% had received prior CDK4/6 inhibitor therapy and ET for more than 12 months. 

The patients were randomly assigned to receive fulvestrant alone (n=55), palbociclib plus fulvestrant (n=111), or avelumab plus palbociclib and fulvestrant (n=54). At a median follow-up of 23.6 months, 18 patients remained on protocol therapy. 

The median PFS was 4.6 months in the palbociclib-fulvestrant arm and 4.8 months in the fulvestrant-alone arm (hazard ratio [HR], 1.11; 90% CI, 0.74-1.66; P =.62). The median PFS was 8.1 months with avelumab plus palbociclib and fulvestrant (HR vs fulvestrant alone, 0.75; 90% CI, 0.47-1.20; P =.23). 

The median overall survival was 24.6 months with palbociclib-fulvestrant and 27.5 months with fulvestrant alone (HR, 1.02; 90% CI, 0.67-1.56). The median overall survival was 42.5 months with avelumab plus palbociclib and fulvestrant (HR vs fulvestrant alone, 0.68; 90% CI, 0.40-1.15).

There were no new safety signals. Neutropenia was the most common grade 3-4 adverse event in the palbociclib-fulvestrant arm (32.7%) and the triplet arm (49.1%). There was no grade 3-4 neutropenia in the fulvestrant arm. 

Dr Mayer noted that rates of immune-related adverse events were low in the triplet arm, and there were no unexpected toxicities in that arm. 

Disclosures: This research was partly supported by Pfizer, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Mayer EL, Ren Y, Wagle N, et al. Palbociclib after CDK4/6i and endocrine therapy (PACE): A randomized phase II study of fulvestrant, palbociclib, and avelumab for endocrine pre-treated ER+/HER2- metastatic breast cancer. Presented at SABCS 2022. December 6-10, 2022. Abstract GS3-06.