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Salgia, Ravi; Weaver, R. Waide; McCleod, Michael; Stille, John R.; Yan, S. Betty; Roberson, Stephanie; Polzer, John; Flynt, Amy; Raddad, Eyas; Peek, Victoria L.; Wijayawardana, Sameera R.; Um, Suzane L.; Gross, Steve; Connelly, Mark C.; Morano, Carrie; Repollet, Madeline; Sanders, Renouard; Baeten, Kurt; D’Haese, David; Spigel, David R.

Prognostic and predictive value of circulating tumor cells and CXCR4 expression as biomarkers for a CXCR4 peptide antagonist in combination with carboplatin-etoposide in small cell lung cancer: exploratory analysis of a phase II study

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  • Medientyp: E-Artikel
  • Titel: Prognostic and predictive value of circulating tumor cells and CXCR4 expression as biomarkers for a CXCR4 peptide antagonist in combination with carboplatin-etoposide in small cell lung cancer: exploratory analysis of a phase II study
  • Beteiligte: Salgia, Ravi; Weaver, R. Waide; McCleod, Michael; Stille, John R.; Yan, S. Betty; Roberson, Stephanie; Polzer, John; Flynt, Amy; Raddad, Eyas; Peek, Victoria L.; Wijayawardana, Sameera R.; Um, Suzane L.; Gross, Steve; Connelly, Mark C.; Morano, Carrie; Repollet, Madeline; Sanders, Renouard; Baeten, Kurt; D’Haese, David; Spigel, David R.
  • Erschienen: Springer Science and Business Media LLC, 2017
  • Erschienen in: Investigational New Drugs
  • Sprache: Englisch
  • DOI: 10.1007/s10637-017-0446-z
  • ISSN: 0167-6997; 1573-0646
  • Schlagwörter: Pharmacology (medical) ; Pharmacology ; Oncology
  • Entstehung:
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  • Beschreibung: <jats:title>Summary</jats:title><jats:p><jats:italic>Background</jats:italic> Circulating tumor cells (CTCs) and chemokine (C-X-C motif) receptor 4 (CXCR4) expression in CTCs and tumor tissue were evaluated as prognostic or predictive markers of CXCR4 peptide antagonist LY2510924 plus carboplatin-etoposide (CE) versus CE in extensive-stage disease small cell lung cancer (ED-SCLC). <jats:italic>Methods</jats:italic> This exploratory analysis of a phase II study evaluated CXCR4 expression in baseline tumor tissue and peripheral blood CTCs and in post-treatment CTCs. Optimum cutoff values were determined for CTC counts and CXCR4 expression in tumors and CTCs as predictors of survival outcome. Kaplan-Meier estimates and hazard ratios were used to determine biomarker prognostic and predictive values. <jats:italic>Results</jats:italic> There was weak positive correlation at baseline between CXCR4 expression in tumor tissue and CTCs. Optimum cutoff values were H-score ≥ 210 for CXCR4<jats:sup>+</jats:sup> tumor, ≥7% CTCs with CXCR4 expression (CXCR4<jats:sup>+</jats:sup> CTCs), and ≥6 CTCs/7.5 mL blood. Baseline H-score for CXCR4<jats:sup>+</jats:sup> tumor was not prognostic of progression-free survival (PFS) or overall survival (OS). Baseline CXCR4<jats:sup>+</jats:sup> CTCs ≥7% was prognostic of shorter PFS. CTCs ≥6 at baseline and cycle 2, day 1 were prognostic of shorter PFS and OS. None of the biomarkers at their respective optimum cutoffs was predictive of treatment response of LY2510924 plus CE versus CE. <jats:italic>Conclusions</jats:italic> In patients with ED-SCLC, baseline CXCR4 expression in tumor tissue was not prognostic of survival or predictive of LY2510924 treatment response. Baseline CXCR4<jats:sup>+</jats:sup> CTCs ≥7% was prognostic of shorter PFS. CTC count ≥6 at baseline and after 1 cycle of treatment were prognostic of shorter PFS and OS.</jats:p>