421P - Changes in cell-free DNA after short-term palbociclib and fulvestrant treatment for advanced or metastatic hormone receptor-positive and human epidermal growth factor 2-negative breast cancer

Background

Here, we investigated the potential predictive and elucidating efficacy of cell-free DNA (cfDNA) changes on clinical outcomes and biological effects, respectively, after short-term palbociclib and fulvestrant treatment for patients with hormone receptor (HR)-positive and human epidermal growth factor 2 (HER2)-negative advanced or metastatic breast cancer (ABC).

Methods

In this secondary analysis of the Japan Breast Cancer Research Group-M07 (FUTURE) trial, blood cfDNA was obtained before palbociclib treatment and on day 15 of cycle one (28-day cycle). Target enrichment was performed using next-generation sequencing; progression-free survival (PFS) was compared based on cfDNA changes between baseline and day 15 of cycle one after combination therapy.

Results

Fifty-six patients (112 paired blood samples) were examined. The median follow-up time was 8.9 months. PIK3CA (30.4%, 17/56), FOXA1 (30.4%, 17/56), and ESR1 (28.6%, 16/56) were most frequently mutated at baseline. The number of mutated genes was significantly decreased on day 15 compared with that at baseline (paired t-test: P-value = 0.025). No significant difference was observed in PFS (decrease group, 7.9 m vs the others, 9.3 m; log-rank P-value = 0.75; hazard ratio, 1.13; 95% confidence interval, 0.53-2.41). Among patients without previous aromatase inhibitor treatment (n = 15), three (20%) had ESR1 mutations after progression to fulvestrant.

Conclusions

No significant association was observed between changes in mutated genes after short-term palbociclib and fulvestrant treatment and disease progression; a significant reduction in cfDNA mutation level was observed on day 15 of cycle one. Clinical meanings of cfDNA should be investigated in the future trials.

Clinical trial identification

The study protocol was registered with the University Hospital Medical Information Network, Japan (UMIN000029294) and Japan Registry of Clinical Trials (CRB2200002).

Editorial acknowledgement

We thank TAKARA bio for the genomic analysis. We greatly appreciate all women who participated in this trial. We also thank all investigators and their collaborators for their dedication to this study, Mebics for their data entry assistance, and the Japan Breast Cancer Research Group (JBCRG) for their administrative assistance.

Legal entity responsible for the study

The authors.

Funding

AstraZeneca K.K.

Disclosure

T. Iwamoto: Financial Interests, Personal, Research Grant: Pfizer. K. Watanabe: Financial Interests, Personal, Speaker’s Bureau: Chugai, Eli Lilly, Nippon-Kayaku, Kyowa-Kirin, Novartis, Taiho, Eisai, Pfizer, Shionogi, Daiichi Sankyo, AstraZeneca. N. Niikura: Financial Interests, Institutional, Research Grant: Chugai, Pfizer; Financial Interests, Institutional, Invited Speaker: Eisai, Mochida, Daiichi Sankyo, Novartis; Financial Interests, Personal, Speaker’s Bureau: Chugai, Eli Lilly, MSD; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, AstraZeneca, Pfizer. Y. Kikawa: Financial Interests, Personal, Speaker’s Bureau: Eisai, Novartis, AstraZeneca, Taiho, Pfizer, Daiichi Sankyo, Lilly, Chugai. K. Kobayashi: Financial Interests, Personal, Speaker’s Bureau: Pfizer, Taiho, Chugai, AstraZeneca, Eli Lilly, Eisai, Novartis. H. Tada: Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo, Eli Lilly, Taiho, Chugai, Pfizer, Novartis, Kirin; Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Eli Lilly, Kirin, Chugai, Novartis, Taiho. U. Toh: Financial Interests, Institutional, Research Grant: Chugai, Eisai, Taiho, Nippon Kayaku; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Kyowa-Kirin, Eli Lilly, Daiichi Sankyo. Y. Yamamoto: Financial Interests, Institutional, Research Grant: Chugai, Kyowa-Kirin, Eisai, Daiichi Sankyo, Nippon-Kayaku, Taiho, Takeda, Lilly, Pfizer, Novartis; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Chugai, Kyowa-Kirin, Novartis, Lilly, Pfizer, Daiichi Sankyo, Nippon-Kayaku, Taiho, Eisai, Takeda, MSD, Sysmex; Financial Interests, Personal, Advisory Board: Exact Science. H. Ishiguro: Financial Interests, Institutional, Research Grant: Eisai, Daiichi Sankyo, Takeda, Chugai; Financial Interests, Personal, Speaker’s Bureau: Eisai, Pfizer, Daiichi Sankyo, Chugai , Kyowa Kirin. N. Masuda: Financial Interests, Institutional, Research Grant: Chugai, Eli Lilly, AstraZeneca, Pfizer, Daiichi Sankyo, MSD, Eisai, Novartis, Sanofi, Kyowa Kirin, Nippon-Kayaku, Ono-Pharma; Financial Interests, Personal, Speaker’s Bureau: Chugai, Pfizer, AstraZeneca, Eli Lilly, Daiichi Sankyo, Eisai. S. Saji: Financial Interests, Institutional, Research Grant: Taiho, Eisai, Chugai, AstraZeneca, Takeda, MSD, Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Chugai, Kyowa Kirin, MSD, Novartis, Eisai, Takeda, Daiichi Sankyo, Eli Lilly, AstraZeneca, Pfizer, Taiho, Ono, Nipponkayaku. All other authors have declared no conflicts of interest.