Analysis of FGFR alterations from circulating tumor DNA (ctDNA) and Tissue in a phase II trial of erdafitinib in urothelial carcinoma (UC)
| Autor: | Ian McCaffery, Peter De Porre, Christopher Moy, Anjali Narayan Avadhani, Matthew V. Lorenzi, Arlene O. Siefker-Radtke, Clifford Motley, Yohann Loriot, Yauheniya Cherkas, Ademi E. Santiago-Walker, Anne OHagan |
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| Rok vydání: | 2019 |
| Předmět: |
musculoskeletal diseases
Cancer Research animal structures Plasma samples business.industry Phases of clinical research 03 medical and health sciences 0302 clinical medicine Oncology Erdafitinib Circulating tumor DNA Fibroblast growth factor receptor 030220 oncology & carcinogenesis Phase (matter) embryonic structures Cancer research Medicine biological phenomena cell phenomena and immunity business 030215 immunology Urothelial carcinoma |
| Zdroj: | Journal of Clinical Oncology. 37:420-420 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2019.37.7_suppl.420 |
| Popis: | 420 Background: Plasma samples from a Phase 2 study of the pan-FGFR inhibitor erdafitinib in advanced UC patients (pts) with FGFR mutations (mut) or fusions, were tested using next generation sequencing (NGS) for circulating tumor DNA (ctDNA), and results compared to central FGFR status determination from tissue. Methods: FGFR alterations were measured in archival tissue using an RNA-based RT-PCR test and compared with FGFR alterations identified in pre-treatment plasma specimens using the Guardant360 ctDNA test. Sensitivity of the ctDNA test to detect the FGFR alterations identified by RT-PCR from tissue, the proportion of pts with a study-eligible FGFR alteration in ctDNA, and the ability to detect a tissue FGFR alteration in ctDNA in relation to clinical response were assessed. Results: Samples from 155 pts with detectable baseline ctDNA were included. Overall, concordance between ctDNA and tissue-based FGFR results was 56% (87/155): 63% (77/122) for tissue mut-positive pts vs 24% (7/29) in fusion-positive pts. 61% of pts (94/155) were positive for a study-eligible FGFR alteration from blood-based testing in the tissue-positive population. The response rate was 47% (36/77) for patients for which FGFR mutations could be detected in blood (ctDNA- FGFR-positive) compared with 32% (14/44) in patients for which mutations were not detected in blood (ctDNA- FGFR-negative), with an estimated odds ratio of 1.882 (95% CI: 0.866; 4.090) Conclusions: The 63% concordance rate for detecting FGFR mut in temporally unmatched blood and tissue supports potential for patient selection with blood-based testing, while ctDNA FGFR fusion detection may require further optimization. Although differences in clinical response rate were observed between ctDNA- FGFR-positive and negative patients, the results were not statistically significant. Importantly, a proportion of ctDNA-negative pts responded to erdafitinib, indicating that tissue-based testing may be warranted for pts negative for FGFR alterations via blood-based testing. (BLC2001, NCT02365597). Clinical trial information: NCT02365597. |
| Databáze: | OpenAIRE |
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