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ePoster Display

615P - Circulating tumor cells (CTC) gene expression and plasma androgen receptor (AR) copy number (CN) in cabazitaxel-treated metastatic castration-resistant prostate cancer (mCRPC)

Date

16 Sep 2021

Session

ePoster Display

Topics

Targeted Therapy;  Cancer Biology;  Translational Research;  Pathology/Molecular Biology

Tumour Site

Prostate Cancer

Presenters

Giorgia Gurioli

Citation

Annals of Oncology (2021) 32 (suppl_5): S626-S677. 10.1016/annonc/annonc702

Authors

G. Gurioli1, V. Conteduca2, N. Brighi2, E. Scarpi3, U. Basso4, G. Fornarini5, A. Mosca6, M. Nicodemo7, G.L. Banna8, C. Lolli2, G. Schepisi2, G. Ravaglia3, P. Ulivi1, U. De Giorgi2

Author affiliations

  • 1 Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 - Meldola/IT
  • 2 Oncology Department, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) “Dino Amadori”, 47014 - Meldola/IT
  • 3 Unit Of Biostatistics And Clinical Trials, IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) “Dino Amadori”, 47014 - Meldola/IT
  • 4 Medical Oncology Unit 1, Istituto Oncologico Veneto IOV IRCCS, 35128 - Padova/IT
  • 5 Medical Oncology Department, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, 16132 - Genova/IT
  • 6 Multidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO-IRCCS, 10060 - Candiolo/IT
  • 7 Medical Oncology, IRCCS Ospedale Sacro Cuore don Calabria, 37138 - Negrar/IT
  • 8 Division Of Medical Oncology, Cannizzaro Hospital, 95126 - Catania/IT

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Abstract 615P

Background

Cabazitaxel showed overall survival (OS) benefit for mCRPC patients (pts) progressing after docetaxel. In a prospective study (NCT03381326), we evaluated the role of CTC gene expression of cabazitaxel-treated pts and its association with plasma AR CN.

Methods

We enrolled 100 mCRPC pts receiving cabazitaxel 20 or 25 mg/sqm from December 2014 to December 2018. Baseline plasma DNA was isolated and digital PCR was performed to assess AR CN status. CTC enrichment was assessed using AdnaTest EMT-2/StemCell kit. CTC expression analyses were performed for 17 genes.

Results

Seventy-four pts were fully evaluable for this analysis. CTC expression of AR-V7 (hazard ratio [HR]=2.52, 95% CI 1.24-5.12, p=0.011), AKR1C3 (HR=2.01, 95% CI 1.06-3.81, p=0.031), AR (HR=2.70, 95% CI 1.46-5.01, p=0.002), EPCAM (HR=3.75, 95% CI 2.10-6.71, p<0.0001), PSMA (HR=2.09, 95% CI 1.19-3.66, p=0.01), MDK (HR=3.35, 95% CI 1.83-6.13, p<0.0001) and HPRT1 (HR=2.46, 95% CI 1.44-4.18, p=0.0009) was associated with shorter OS in univariate analysis. ALDH1 (odds ratio [OR]=5.50, 95% CI 0.97-31.22, p=0.05), AR (OR=8.71, 95% CI 2.32-32.25, p=0.001), EPCAM (OR=7.26, 95% CI 1.47-35.73, p=0.015), PSMA (OR=3.86, 95% CI 1.10-13.50, p=0.035), MDK (OR=6.84, 95% CI 1.87-24.98, p=0.004) and HPRT1 (OR=7.41, 95% CI 1.82-30.19, p=0.005) expression was associated with early disease progression within the first three months. AR CN status was correlated with AR-V7 (p=0.05), EPCAM (p=0.02) and MDK (p=0.002) expression. Using a multivariable model, EPCAM CTC expression, AR CN gain, ECOG PS ≥ 2 and liver metastases were independently associated with poorer OS. In pts treated with cabazitaxel 20 mg/sqm, a shorter median OS was observed in AR-V7-pos pts (n=8) than AR-V7-neg (n=36) (6.6 versus 14 months, HR=3.46, 95% CI 1.47-8.17, p=0.004). No significant difference was found between those patients treated with cabazitaxel 25 mg/sqm (p=0.839).

Conclusions

Baseline CTC biomarkers may be considered useful prognosticators for cabazitaxel-treated mCRPC pts. Our results suggest that cabazitaxel 25 mg/sqm should be preferred in AR-V7-pos mCRPC.

Clinical trial identification

NCT03381326.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Partially funded by Sanofi Genzyme.

Disclosure

G. Gurioli: Other, Institutional, Other, Travel support: Sanofi Genzyme. V. Conteduca: Other, Institutional, Advisory Board: Janssen; Other, Institutional, Advisory Board: Astellas; Other, Institutional, Advisory Board: Merck; Other, Institutional, Advisory Board: AstraZeneca; Other, Institutional, Advisory Board: Bayer; Other, Institutional, Other, travel support: Ipsen; Other, Institutional, Other, travel support: Sanofi Genzyme. N. Brighi: Other, Institutional, Other, Travel support: Pfizer; Other, Institutional, Other, Travel support: Ipsen; Other, Institutional, Other, Travel support: Novartis. G. Fornarini: Other, Institutional, Advisory Role: Ipsen; Other, Institutional, Advisory Role: Sanofi Genzyme; Other, Institutional, Advisory Role: BMS; Other, Institutional, Advisory Role: Pfizer; Other, Institutional, Advisory Role: Janssen; Other, Institutional, Advisory Role: MSD; Other, Institutional, Advisory Role: Novartis. M. Nicodemo: Other, Institutional, Other: Bristol-Myers Squibb; Other, Institutional, Other: Ipsen; Other, Institutional, Other: Molteni; Other, Institutional, Other: Janssen. G.L. Banna: Other, Personal, Other: Janssen-Cilag; Other, Personal, Other: Boehringer Ingelheim; Other, Personal, Other: Roche; Other, Personal, Other: AstraZeneca/MedImmune. C. Lolli: Other, Institutional, Advisory Board: Bristol-Myers Squibb; Other, Institutional, Advisory Board: Janssen-Cilag. U. De Giorgi: Other, Institutional, Advisory Board: Astellas; Other, Institutional, Advisory Board: Bayer; Other, Institutional, Advisory Board: BMS; Other, Institutional, Advisory Board: Ipsen; Other, Institutional, Advisory Board: Janssen; Other, Institutional, Advisory Board: Merck; Other, Institutional, Advisory Board: Pfizer; Other, Institutional, Advisory Board: Sanofi Genzyme; Other, Institutional, Research Grant: AstraZeneca; Other, Institutional, Research Grant: Roche. All other authors have declared no conflicts of interest.

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