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Exploratory biomarker analyses from ECOG 4508: Three-arm randomized phase II study of carboplatin (C) and paclitaxel (P) in combination with cetuximab (CET), IMC-A12, or both for advanced non-small cell lung cancer (NSCLC) patients (pts)
Abstract   Open access   Peer reviewed

Exploratory biomarker analyses from ECOG 4508: Three-arm randomized phase II study of carboplatin (C) and paclitaxel (P) in combination with cetuximab (CET), IMC-A12, or both for advanced non-small cell lung cancer (NSCLC) patients (pts)

Charu Aggarwal, Suzanne Eleanor Dahlberg, Nasser Hanna, Jill Kolesar, Fred R. Hirsch, Suresh S. Ramalingam and Joan H. Schiller
Journal of clinical oncology, Vol.31(15_suppl), pp.8106-8106
05/20/2013
DOI: 10.1200/jco.2013.31.15_suppl.8106
url
https://doi.org/10.1200/jco.2013.31.15_suppl.8106View
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Abstract

Abstract only 8106 Background: ECOG 4508 was a phase II study that randomized advanced NSCLC pts that were not candidates for bevacizumab to receive: C + P iv on day 1 every 3 wks with either CET iv weekly (arm A, n=39), IMC-A12 iv every 2 wks (arm B, n=42), or both (arm C, n=48). The study was closed prematurely due to safety concerns after 129 eligible pts were treated. The study failed to meet its primary objective (Hanna et al ASCO 2012). Methods: Tumor samples were analyzed by immunohistochemistry (IHC; EGFR, IGF-1R and IGF-2R expression), fluorescent in-situ hybridization (FISH; EGFR gene copy number) and DNA sequencing (EGFR, KRAS gene mutations). Time-to-event distributions were estimated using the Kaplan-Meier method, and differences were tested using the logrank test. Cox proportional hazards models were fitted to estimate hazard ratios. Results: Histology: 38% squamous cell, 39% adenocarcinoma, 2% BAC, 5% NOS and 6% other. OS was similar in EGFR FISH+ (Colorado classification system, n=30/70, 43%) vs EGFR FISH- pts (57%), (9.5 mos vs 8.6 mos, HR=0.62, p=0.08). For EGFR FISH+ pts, there was no difference in outcomes with CET (n=19, OS=9.7 mos, PFS=4.1 mos) vs no CET (n=11, OS=9.5 mos, PFS=5.5 mos). EGFR and KRAS mutations were detected in 6% (5/80) and 22% (6/27) of the pts respectively, but sample sizes were not large enough for robust testing. EGFR and IGFR IHC hybrid (H) scores were assessed on 98/102 available samples (Arm A=29, Arm B=34, Arm C=35). Median H scores (and range): IGF-1R: 190 (30-390), IGF-2R: 145 (20-350), EGFR membrane and cytoplasm: 190 (0-380) and EGFR membrane only: 160 (0-390). With IGF-1R and IGF-2R H score > 200, there was no association with OS (HR 1.3, p=0.26; HR 1.4, p=0.28) or PFS (HR=1.1, p=0.67; HR=1.2, p=0.56), adjusted for whether or not IMCA12 was received. Similarly, no associations with OS or PFS were seen with EGFR membrane H score > 200, adjusted for CET administration (OS HR=0.89, p=0.64; PFS HR 1.1, p=0.62). Conclusions: There was no correlation between EGFR FISH or H score and outcomes with CET. IGF-1R and IGF-2R expression was not predictive of favorable outcome with IMC-A12. Clinical trial information: NCI-2011-01976.

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