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Circulating-free DNA (cfDNA) as biomarker of taxane resistance in metastatic castration-resistant prostate cancer (mCRPC)
Abstract   Open access   Peer reviewed

Circulating-free DNA (cfDNA) as biomarker of taxane resistance in metastatic castration-resistant prostate cancer (mCRPC)

Edoardo Francini, Fang-Shu Ou, Justin Rhoades, Eric G. Wolfe, Edward O'Connor, Gavin Ha, Gydush Gregory, Kaitlin Kelleher, Rupal Satish Bhatt, Steven P. Balk, …
Journal of clinical oncology, Vol.38(6_suppl), pp.174-174
02/20/2020
DOI: 10.1200/JCO.2020.38.6_suppl.174
url
https://doi.org/10.1200/JCO.2020.38.6_suppl.174View
Published (Version of record) Open Access

Abstract

Abstract only 174 Background: Docetaxel (D) and cabazitaxel (C) are standard chemotherapies for mCRPC. A reliable biomarker predictive of resistance to D or C is yet to be identified. We aimed to assess the association between genetic amplification of the multidrug resistance transporter ABCB1 (ABCB1 amp) and primary resistance (RES) to D or C for mCRPC, using cfDNA. Methods: A cohort (A) of 136 patients (pts) with at least 1 plasma sample drawn and stored within 1 year prior to starting D for mCRPC (2002-2014) and a cohort (B) of 42 pts with at least 1 plasma sample from within 1 year prior to starting C for mCRPC (2010-2016) were identified from the Dana-Farber Cancer Institute IRB approved database. Whole genome sequencing (WGS) at 0.1x coverage, termed ultra-low pass WGS (ULP-WGS), was performed on cfDNA extracted from the selected samples (1000μL/subject) and sequencing data were analyzed using a tool called ichorCNA to identify cases with sufficient tumor DNA content (>7%) for accurate detection of copy number alterations (CNAs) including ABCB1 amp. Primary objective was the association between ABCB1 amp and RES to D or C. RES was defined as lack of response (no PSA50 decline or radiologic response per RECIST criteria 1.1, within 4 months from treatment start). Odds ratio (OR) was used to compare odds of RES to D or C for pts with ABCB1 amp and P-values were calculated by Fisher’s exact test. Results: Of the selected 178 pts, 66 had tumor fraction >7%: 45 pts in cohort A and 21 in cohort B. No significant association was noted between ABCB1 amp and RES to D (P=0.7123; OR=1.600) or C (P=1.000; OR=1.0606). RES was observed in 26 pts (57.8%) of cohort A and 18 (85.7%) of cohort B. ABCB1 amp was found in 9 pts (20%; 95% CI, 9.6-34.6) in group A and 6 of them (66%) had RES to D. ABCB1 amp rate among D-resistant men was 23.1% (95% CI, 9.0-43.7). In group B, 2 pts (9.5%; 95% CI, 1.2-30.4) had ABCB1 amp and both of them had RES to C. ABCB1 rate among C-resistant pts was 11.1% (95% CI, 1.4-34.7). Conclusions: In this study, ABCB1 amp using cfDNA did not show statistically significant correlation with RES to D or C for pts with mCRPC. Future studies including ABCB1 amp in a suite of putative biomarkers and larger sample size may aid drawing definitive conclusions.

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