First-line (1L) panitumumab (PAN) vs bevacizumab (BEV) in patients (pts) with HER2 amplification (HER2amp+), RAS wild type (WT) metastatic colorectal cancer (mCRC) according to tumor sidedness.

Abstract

53 Background: HER2 gene alterations occur in 3%–5% of pts with mCRC and may be associated with aggressive tumor behavior. Gene amplification is a frequent HER2 alteration in mCRC, often leading to HER2 protein overexpression. Preclinical and retrospective studies suggest HER2 alterations may predict anti–epidermal growth factor receptor (EGFR) therapy resistance in mCRC; however, there is limited information regarding the efficacy of 1L anti-EGFR therapy in mCRC pts with HER2 alterations. The PARADIGM trial demonstrated longer median OS with 1L PAN (anti-EGFR) vs BEV (anti–vascular endothelial growth factor), with mFOLFOX6, in RAS WT mCRC (NCT02394795). We evaluated the efficacy of PAN vs BEV in pts with HER2amp + and HER2amp−, RAS WT mCRC from PARADIGM, taking into account primary tumor sidedness. Methods: Baseline plasma ctDNA was obtained from pts with RAS WT mCRC enrolled in PARADIGM; pts with evaluable pretreatment ctDNA were included in the biomarker analysis (NCT02394834). A custom panel (PlasmaSELECT-R 91, PGDx) was used to detect HER2amp+ and HER2amp− samples. OS, PFS, and response rate (RR) were compared in pts with HER2amp+ vs pts with HER2amp−. Results: Of 802 pts with RAS WT mCRC, 733 (91%) had evaluable pretreatment samples; 32 (4%) had HER2amp + (PAN, n=19; BEV, n=13). A lack of a survival benefit with PAN vs BEV was suggested in pts with HER2amp+, regardless of tumor-sidedness (median OS: overall population, PAN, 23.0 mo; BEV, 26.7 mo; HR, 0.96; 95% CI: 0.45–2.04; left-sided population, PAN, 25.1 mo; BEV, 26.7 mo; HR, 0.89; 95% CI: 0.39–2.04]). Data in the right-sided population are not shown for pts with HER2amp+ due to the small sample size. In the overall population, there was a trend toward shorter OS for HER2amp + vs HER2amp− pts (PAN: 23.0 vs 36.3 mo; HR, 1.57; 95% CI: 0.96–2.57; BEV: 26.7 vs 31.6 mo; HR, 1.41; 95% CI: 0.79–2.52). Median PFS and RR were similar between pts with HER2amp + and HER2amp− in PAN or BEV arms (Table). Conclusions: HER2 amplification appears to be prognostic in pts with RAS WT mCRC but may not be predictive of a survival benefit of 1L PAN treatment over BEV. Clinical trial information: NCT02394834 . [Table: see text]