Journal Article

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

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

2017

Overview

Summary Background 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). Methods 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. Results There was weak positive correlation at baseline between CXCR4 expression in tumor tissue and CTCs. Optimum cutoff values were H-score ≥ 210 for CXCR4 + tumor, ≥7% CTCs with CXCR4 expression (CXCR4 + CTCs), and ≥6 CTCs/7.5 mL blood. Baseline H-score for CXCR4 + tumor was not prognostic of progression-free survival (PFS) or overall survival (OS). Baseline CXCR4 + 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. Conclusions In patients with ED-SCLC, baseline CXCR4 expression in tumor tissue was not prognostic of survival or predictive of LY2510924 treatment response. Baseline CXCR4 + 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.

• Publisher: Springer US,Springer Nature B.V
• Subject: Antagonist drugs / Antineoplastic Agents - pharmacology / Antineoplastic Agents - therapeutic use / Antineoplastic Combined Chemotherapy Protocols - pharmacology / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Biomarkers / Biomarkers, Tumor - blood / Cancer / Carboplatin / Carboplatin - pharmacology / Carboplatin - therapeutic use / Cell Count / CXCR4 protein / Disease-Free Survival / Etoposide / Etoposide - pharmacology / Etoposide - therapeutic use / Humans / Kaplan-Meier Estimate / Lung cancer / Lung diseases / Lung Neoplasms - blood / Lung Neoplasms - drug therapy / Lung Neoplasms - metabolism / Medical prognosis / Medicine / Medicine & Public Health / Neoplastic Cells, Circulating / Oncology / Peptides / Peptides, Cyclic - pharmacology / Peptides, Cyclic - therapeutic use / Peripheral blood / Pharmacology/Toxicology / Phase II Studies / Prognosis / Receptors, CXCR4 - antagonists & inhibitors / Receptors, CXCR4 - metabolism / Small cell lung carcinoma / Small Cell Lung Carcinoma - blood / Small Cell Lung Carcinoma - drug therapy / Small Cell Lung Carcinoma - metabolism / Studies / Survival / Tumor cells / Tumors