Abstract 2774: Correlative analysis of systemic markers from a randomized trial assessing local consolidative therapy for non-small cell lung cancer (NSCLC) patients with oligometastatic disease
Authors: Tang Chad , Heymach John V. , Reuben Alexandre , Tran Hai , Welsh James , Wargo Jennifer , Liao Zhongxing , Tsao Anne , Prado Eric , Swisher Stephen , Zhang Jianjun , Gomez Daniel 
Published: July 2017

Introduction: We present serum correlative analysis from a phase II randomized trial to identify markers associated with progression free survival (PFS) in NSCLC.

Methods: NSCLC patients presenting with oligometastatic disease (≤3 metastases) were enrolled on a multi-institution phase II randomized trial (NCT01725165). Patients who did not progress after ≥3 months of first-line systemic therapy were randomized to upfront local consolidative therapy (LCT arm) to all sites of disease or at later progression (no-LCT arm). For correlative analyses, peripheral blood was collected from consenting patients after completion of initial systemic therapy but prior to randomization (baseline) and at each follow up. Serum cytokine and angiogenesis factors (CAFs) were analyzed via magnetic bead-based multiplex assay (Merck Millipore). Peripheral blood T cell receptor (TCR) repertoire was profiled by immunoSEQ (Adaptive Biotechnologies). Peripheral cell-free DNA (cfDNA) was subjected to next generation sequencing of a panel of cancer genes. Comparisons of PFS, the primary endpoint of this study, were conducted via log-rank test.

Results: After enrollment of 74 patients with a median follow up of 19 months, this study was closed early after the Data Safety Monitoring Committee review determined efficacy in the LCT arm. Of 49 randomized patients, correlative blood draws were conducted on 33 patients. Considering all patients, high baseline EGF (cutpoint 50 pg/ml; median PFS: 5.7 vs 19.8 mo), Eotaxin (cutpoint 110 pg/ml; median PFS: 5.7 vs 21 mo), TNF alpha (cutpoint 8 pg/ml; median PFS: 3.6 vs 17.9 mo), or low baseline GRO (cutpoint 600 pg/ml; median PFS: 17.9 vs 3.6 mo) were associated with longer PFS (all P&lt;0.05). When considering individual treatment arms, LCT arm patients exhibiting low baseline MMP-2 (cutpoint 90 ug/ml; median PFS: 17.9 vs 5.3 mo) and no-LCT arm patients exhibiting low baseline GRO (cutpoint 600 pg/ml; median PFS: 21.0 vs 1.8 mo) or high baseline FGF-2 (cutpoint 58 pg/ml; median PFS: 2.2 vs 21.0 mo) exhibited longer PFS (all P&lt;0.05). TCR repertoire and cfDNA profile analyses are underway.

Conclusions: In this exploratory analysis, we identified baseline CAFs associated with PFS. These finding are being validated in a larger cohort of patients. If validated, CAFs could be a biomarker to select patients with oligometastatic NSCLC for aggressive local treatment.

Citation Format: Chad Tang, John V. Heymach, Alexandre Reuben, Hai Tran, James Welsh, Jennifer Wargo, Zhongxing Liao, Anne Tsao, Eric Prado, Stephen Swisher, Jianjun Zhang, Daniel Gomez. Correlative analysis of systemic markers from a randomized trial assessing local consolidative therapy for non-small cell lung cancer (NSCLC) patients with oligometastatic disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2774. doi:10.1158/1538-7445.AM2017-2774