1 Grothey A, et al. ESMO Open 2018;3:e000347. doi:10.1136/esmoopen-2018-000347 Open Access Association of baseline absolute neutrophil counts and survival in patients with metastatic colorectal cancer treated with second-line antiangiogenic therapies: exploratory analyses of the RAISE trial and validation in an electronic medical record data set Axel Grothey, 1 Takayuki Yoshino, 2 Gyorgy Bodoky, 3 Tudor Ciuleanu, 4 Rocio Garcia-Carbonero, 5 Pilar García-Alfonso, 6 Eric Van Cutsem, 7 Kei Muro, 8 Daniel S Mytelka, 9 Li Li, 10 Olga Lipkovich, 10 Yanzhi Hsu, 10 Andreas Sashegyi, 10 David Ferry, 10 Federico Nasroulah, 11 Josep Tabernero 12 Original research ► Additional material is published online only. To view please visit the journal online (http://dx.doi.org/10.1136/ esmoopen-2018-000347). To cite: Grothey A, Yoshino T, Bodoky G, et al. Association of baseline absolute neutrophil counts and survival in patients with metastatic colorectal cancer treated with second- line antiangiogenic therapies: exploratory analyses of the RAISE trial and validation in an electronic medical record data set. ESMO Open 2018;3:e000347. doi:10.1136/ esmoopen-2018-000347 Received 1 March 2018 Revised 20 March 2018 Accepted 21 March 2018 For numbered affliations see end of article. Correspondence to Dr Josep Tabernero; jtabernero@vhio.net ABSTRACT Background In the RAISE trial, ramucirumab+leucovorin/ fuorouracil/irinotecan (FOLFIRI) improved the median overall survival (mOS) of patients with previously treated metastatic colorectal cancer versus patients treated with placebo+FOLFIRI but had a higher incidence of neutropaenia, leading to more chemotherapy dose modifcations and discontinuations. Thus, we conducted an exploratory post-hoc analysis of RAISE and a retrospective, observational analysis of electronic medical record (EMR) data to determine and verify the association of neutropaenia, baseline absolute neutrophil count (ANC) and survival. Methods The RAISE analysis used the study safety population (n=1057). IMS Health Oncology Database (IMS EMR) was the source for the real-world data set (n=617). Results RAISE patients with treatment-emergent neutropaenia had improved mOS compared with those without (ramucirumab arm: 16.1 vs 10.7 months, HR=0.57, p<0.0001; placebo arm: 12.7 vs 10.7 months, HR=0.76, p=0.0065). RAISE patients with low ANC versus high baseline ANC also had longer mOS (ramucirumab arm: 15.2 vs 8.9 months, HR=0.49, p<0.0001; placebo arm: 13.2 vs 7.3 months, HR=0.50, p<0.0001). The results were similar for IMS EMR low versus high baseline ANC (bevacizumab+FOLFIRI patients: 14.9 vs 7.7 months, HR=0.59, p<0.0001; FOLFIRI alone: 14.6 vs 5.4 months, HR=0.37, p<0.0001). Patients in the RAISE trial with low baseline ANC were more likely to develop neutropaenia (OR: ramucirumab arm=2.62, p<0.0001; placebo arm=2.16, p=0.0003). Conclusion Neutropaenia during treatment, and subsequent dose modifcations or discontinuations, do not compromise treatment effcacy. Baseline ANC is a strong Key questions What is already known about this subject? ► Historically, the second-line treatment choice in patients with metastatic colorectal cancer (mCRC) has depended on the treatment administered as frst-line therapy. ► However, ideally the decisions of which therapy to prescribe as second-line treatment and when to discontinue or change treatment, based on a lack of effcacy and/or high toxicity, would be informed from reliable predictive or prognostic biomarkers. ► Although therapy options for mCRC have increased, valuable predictive and prognostic markers of treatment effcacy remain largely unidentifed. ► Neutropaenia has previously been characterised as a prognostic factor for cancer treatment effcacy. What does this study add? ► An association between neutropaenia incidence and better overall survival was determined in patients with mCRC from the ramucirumab RAISE trial. ► Baseline absolute neutrophil count was confrmed as a prognostic marker for survival in previously treated patients with colorectal cancer in a post-hoc analysis of the RAISE trial and confrmed in a prespecifed analysis using electronic medical record data.