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Found 2 Presentations For Request "Abs: 650P"
650P - Comparing the predictive value of exosome, circulating tumor cells, and tumor tissue in detecting AR-V7 among metastatic castration-resistant prostate cancer treated with abiraterone
- Sha Zhu (Chengdu, China)
Abstract
Background
Androgen Receptor Splice Variant-7 (AR-V7) can predict primary and secondary resistance to abiraterone in metastatic castration-resistant prostate cancer (mCRPC). However, the predictive value of different AR-V7 detecting methods (plasma-derived exosome, circulating tumor cells (CTCs), and tumor tissue) has never been compared.
Methods
Matched whole blood and tumor tissue from 23 mCRPC patients was collected prior to the initiation of abiraterone. Exosomes were extracted from plasma and analyzed for AR-V7 mRNA expression by digital droplet polymerase chain reaction (ddPCR). CTCs were extracted and analyzed for AR-V7 mRNA expression by RNA in situ hybridization (RISH). AR-V7 protein expression in prostate cancer tissue was determined by immunohistochemistry (IHC). Circulating tumor DNA (ctDNA) was also extracted and analyzed by 90-gene next-generation sequencing (NGS). The primary outcome is biochemical progression-free survival (b-PFS).
Results
AR-V7 was positive in 39.1% (n=9/23), 36.4% (n=4/11) and 21.7% (n=5/23) patients evaluated with plasma-derived exosome, CTC and tumor tissue, respectively. The concordance of AR-V7 status between exosome and tumor tissue was 65.2%, while the concordance between CTC and tumor tissue was 72.7%. Positive AR-V7 detected in exosome was associated with shorter bPFS compared with AR-V7 negative patients (HR 4.08, 95%CI 1.13-14.69, P=0.03). However, AR-V7 positivity in tumor tissue and CTC failed to predict clinical prognosis in mCRPC treated with abiraterone (AR-V7 detected in CTC: HR 1.00, 95%CI 0.24-4.18, P=0.74; AR-V7 detected in tumor tissue: HR 1.16, 95%CI 0.32-4.16, P=0.97). Genomic alterations in the AR pathway (AR, FOXA1, NCOR1, NCOR2, ZBTB16) were detected in 71.4% patients, who had inferior bPFS (HR 3.56, 95%CI 1.13-11.18, log-rank P=0.03) compared with those with AR pathway of wildtype.
Conclusions
The concordance of AR-V7 status between plasma-derived exosomes, CTCs, and tumor tissue is moderate. The positivity of AR-V7 in plasma-derived exosomes outperforms CTC and tumor tissue as a predictor of primary resistance in mCRPC patients treated with abiraterone.
Legal entity responsible for the study
Hao Zeng.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
1165P - Subgroup analysis by Ki-67 and primary tumour origins of the randomized, placebo-controlled phase III study of surufatinib in advanced well-differentiated extrapancreatic neuroendocrine tumours (SANET-ep)
- Zhiwei Zhou (Guangzhou, China)
Abstract
Background
Surufatinib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptors (1,2,3), fibroblast growth factor receptor 1 and colony stimulating factor 1 receptor, has demonstrated superior efficacy in extrapancreatic neuroendocrine tumors (NETs) in a phase III study (SANET-ep, ESMO 2019 Abs. LBA76). The proliferation marker Ki-67 and primary tumor origins are the major prognostic factors in NETs.
Methods
The post-hoc efficacy analysis of surufatinib versus placebo was conducted by Ki-67 subcategory (<3%, 3-10%, >10%) and primary tumor origins (foregut, midgut, hindgut, others or unknown) in patients (pts) with advanced well-differentiated (grade 1 or 2) extrapancreatic NETs. The primary endpoint (progression-free survival [PFS]) and secondary endpoint (objective response rate [ORR]) both by investigator assessment (RECIST1.1) were analyzed.
Results
Median PFS was significantly prolonged with surufatinib compared to placebo in subgroups of Ki-67 3-10% (7.6 vs 4.6 months [mo], hazard ratio [HR] 0.47,
Conclusions
Surufatinib demonstrated clinically significant benefits for pts with advanced well-differentiated extrapancreatic NETs compared to placebo. Results of this exploratory analysis were consistent with those reported for the SANET-ep primary analysis, and improved outcomes were observed across major subgroups.
Clinical trial identification
NCT02588170.
Legal entity responsible for the study
Hutchison MediPharma Limited.
Funding
Hutchison MediPharma Limited.
Disclosure
J. Li, J. He: Full/Part-time employment: Hutchison MediPharma Limited. W. Su: Shareholder/Stockholder/Stock options, Full/Part-time employment: Hutchison MediPharma Limited. All other authors have declared no conflicts of interest.