Abstract A032: Circulating tumor (ct)DNA mutations in EGFR pathway genes and clinical outcomes for patients with metastatic colorectal cancer (mCRC) treated with panitumumab from the ASPECCT study

• Published in: Molecular cancer therapeutics 2018-01, Vol.17 (1_Supplement), p.A032-A032
• Main Authors: Boedigheimer, Michael, Ang, Agnes Lee, Kim, Tae Won, Thomas, Anne, Gibbs, Peter, Ruff, Paul, Hool, Kristina, Price, Timothy
• Format: Article
• Language: English
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.TARG-17-A032

Background: Mutations in RAS family genes are a negative predictor for response to anti-EGFR therapy. ASPECCT was the first prospective study to show that panitumumab was noninferior to cetuximab for overall survival (OS) in chemorefractory wild-type (WT) KRAS exon 2 mCRC. This analysis used next-generation sequencing of ctDNA before and after panitumumab therapy to explore mutations in EGFR pathway genes and their association with outcomes. Methods: Plasma samples collected at baseline (BL) and safety follow-up (SFU) were analyzed for ctDNA mutations using the PlasmaSelect-R™ 63-gene panel. Mutations for six major genes within the EGFR pathway (BRAF, KRAS, MAP2K1, NRAS, PIK3CA, and PTEN) were analyzed as categorical and continuous variables, and were evaluated for association with OS using univariate Cox proportional hazards (PH) model. Results: Of the 499 patients randomized to panitumumab, 208 had paired plasma samples at BL and SFU. Of the 113 (54.3%) patients who were WT for all genes at BL, 59 (52%) remained WT at SFU. At BL, 65 patients had single gene mutations in either BRAF (7.7%), KRAS (6.7%), PIK3CA (6.3%), NRAS (5.8%), PTEN (3.8%), or MAP2K1 (1.0%), and 30 patients had mutations in multiple genes (at