Background

POLARIS is an ongoing, prospective, real-world (RW) study of palbociclib (PAL) in patients (pts) with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- ABC). A biomarker goal of this study was to evaluate serial changes in circulating tumor DNA (ctDNA) dynamics among pts with long-term clinical response to PAL plus endocrine therapy (ie, received ≥18 cycles).

Methods

The data set included pts who received PAL combination therapy, gave consent for blood collection to obtain ctDNA, and had long-term clinical response. The Guardant360 Next-Generation Sequencing platform, which analyzed approximately 73 genes, was used to sequence ctDNA for somatic single-nucleotide variants, including copy number variants. Longitudinal ctDNA changes (at baseline and various time points) and the RW clinical response to PAL are described.

Results

As of December 17, 2020, 35 pts of 1280 enrolled received ≥18 cycles of PAL combination therapy, with blood samples collected over a minimum of a 24-month period. Pts received PAL plus an aromatase inhibitor (n=16) or fulvestrant (n=19). Median age was 64 years. Thirty pts (85.7%) were white, 29 (82.9%) were postmenopausal, 31 (88.6%) had an Eastern Cooperative Oncology Group score of 0 or 1, 12 (34.3%) had visceral disease, 9 (25.7%) had de novo disease, and 24 (68.6%) had recurrent disease. Six pts (17.1%) had a RW best overall response (BOR) of complete response (CR), 9 (25.7%) had partial response (PR), and 20 (57.1%) had stable disease (SD). Two pts had disease progression resulting in change of therapy at cycles 25 and 38, respectively. Biomarker samples were collected from a median (range) total number of 9 (3-12) visits. The median (range) number of somatic variants detected was 4 (0-11) and included the most prevalent somatic mutations (eg, PIK3CA, TP53, BRCA1/2, FGFR2, GATA3). No ctDNA mutations were detected in 6 pts (17%) post baseline up to 24 months. Among 15 pts who achieved CR/PR, 12 (80%) either had no detectable or sustained very low ctDNA burden or had corresponding ctDNA decrease. Among 16 pts who remained with SD, 12 (75%) either had no detectable or sustained very low ctDNA burden or had ctDNA decrease. Among 8 pts whose disease progressed, 5 (63%) had an increasing trend in ctDNA mutation frequency.

Conclusions

This study is among the first to provide serial blood-based tumor genotyping data from routine clinical practice. Interim data indicate that even pts with ongoing detectable ctDNA have a BOR of CR, PR, or SD with PAL for HR+/HER2- ABC, suggesting certain mutations might not be drivers of PAL resistance. Dynamic changes of ctDNA mutations may be predictive for treatment response, and may have clinical utility in disease surveillance monitoring. Additional longitudinal data will be presented.

Pfizer; NCT03280303

Citation Format: Joanne L. Blum, Aditya Bardia, Sharon Wilks, Steven L. McCune, Carrie L. Dul, John J. Migas, Derrick W. Spell, Zhe Zhang, Yuan Liu, Yao Wang, Debu Tripathy. Longitudinal ctDNA changes in patients with long-term response to palbociclib combination therapy for advanced breast cancer: A preliminary analysis from the real-world POLARIS study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB033.