Early Tumor Shrinkage and Depth of Response in the Second-Line Treatment for KRAS exon2 Wild-Type Metastatic Colorectal
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ORIGINAL RESEARCH ARTICLE
Early Tumor Shrinkage and Depth of Response in the Second‑Line Treatment for KRAS exon2 Wild‑Type Metastatic Colorectal Cancer: An Exploratory Analysis of the Randomized Phase 2 Trial Comparing Panitumumab and Bevacizumab in Combination with FOLFIRI (WJOG6210G) Naoki Izawa1 · Kohei Shitara2 · Kimio Yonesaka3 · Takeharu Yamanaka4 · Takayuki Yoshino2 · Yu Sunakawa1 · Toshiki Masuishi5 · Tadamichi Denda6 · Kentaro Yamazaki7 · Toshikazu Moriwaki8 · Hiroyuki Okuda9 · Chihiro Kondoh10 · Tomohiro Nishina11 · Akitaka Makiyama12,13 · Hideo Baba14 · Hironori Yamaguchi15 · Masato Nakamura16 · Ichinosuke Hyodo8 · Kei Muro5 · Takako Eguchi Nakajima1,17
© Springer Nature Switzerland AG 2020
Abstract Background Predictive markers for the clinical outcomes of second-line treatment in patients with metastatic colorectal cancer (mCRC) remain unclear. Objective This retrospective biomarker study was conducted to explore predictive markers for patients with KRAS exon 2 wild-type mCRC who were treated with FOLFIRI plus panitumumab (Pani) or bevacizumab (Bev) in the WJOG6210G trial. Patients and methods The associations of early tumor shrinkage (ETS), tumor location, and VEGF-D with progression-free survival (PFS) and overall survival (OS) were analyzed using a Cox proportional hazards model. Spearman’s correlation coefficient was used to analyze the association of depth of response (DpR) with PFS and OS. Serum VEGF-D levels were measured in samples collected before treatment using magnetic bead panel Milliplex xMAP kits. Results In total, 101 patients (Pani, n = 49; Bev, n = 52) were enrolled in this study. Patients with ETS had longer PFS (Pani: hazard ratio (HR) 0.40, P = 0.009; Bev: HR 0.078, P = 0.0002) and OS (Pani: HR 0.49, P = 0.044; Bev: HR 0.35, P = 0.048) than patients without ETS. The DpR was moderately correlated with PFS and OS in Pani (rs = 0.75, P
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