Background. There is a patent need to better characterize early-stage colorectal cancer (CRC) patients. PD-1 ligand (PD-L1) expression has been proposed as a prognostic factor but yields mixed results in different settings. The Consensus Molecular Subtype (CMS) classification has yet to be integrated into clinical practice. We sought to evaluate the prognostic value of PD-L1 expression overall and within CMS in early-stage colon cancer patients, in the hope of assisting treatment choice in this setting. Methods. Tissue-microarrays were constructed from tumor samples of 162 stage II/III CRC patients. They underwent automatic immunohistochemical staining for PD-L1 and the proposed CMS panel. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Results. PD-L1 expression was significantly and independently associated with better prognosis (HR = 0.46 (0.26–0.82), p = 0.009) and was mostly seen in immune cells of the tumor-related stroma. CMS4 five-folds the risk of mortalitycompared with CMS1 (HR = 5.58 (1.36, 22.0), p = 0.034). In the subgroup CMS2/CMS3 analysis, PD-L1 expression significantly differentiated individuals with better OS (p = 0.004) and DFS (p < 0.001). Conclusions. Our study suggests that PD-L1 expression is an independent prognostic factor in patients with stage II/III colon cancer. Additionally, it successfully differentiates patients with better prognosis in the CMS2/CMS3 group and may prove significant for the clinical relevance of the CMS classification.

Background: Metastatic gastric cancer and cancer of the esophagogastric junction (GC/EGJ) is an aggressive disease with poor prognosis. In the TAGS study, trifluridine/tipiracil (FTD/TPI) improved overall survival (OS) compared with placebo in heavily pre-treated patients. This unplanned, exploratory subgroup analysis of the TAGS study aimed to clarify outcomes when FTD/TPI was used as third-line (3L) treatment and fourth-or later-line (4Lþ) treatment. Patients and methods: Patients were divided into a 3L group (126 and 64 in FTD/TPI and placebo arms, respectively) and 4Lþ group (211 and 106 in FTD/TPI and placebo arms, respectively). Endpoints included OS, progression-free survival (PFS), time to Eastern Cooperative Oncology Group performance status (ECOG PS) deterioration to !2, and safety. Results: Baseline characteristics were generally well balanced between FTD/TPI and placebo for 3L and 4Lþ treatment. Median OS (mOS) for FTD/TPI versus placebo was: 6.8 versus 3.2 months {hazard ratio (HR) [95% confidence interval (CI)] ¼ 0.68 (0.47-0.97), P ¼ 0.0318} in the 3L group; and 5.2 versus 3.7 months [0.73 (0.55-0.95), P ¼ 0.0192] in the 4Lþ group. Median PFS for FTD/TPI versus placebo was 3.1 versus 1.9 months [0.54 (0.38-0.77), P ¼ 0.0004] in the 3L group; and 1.9 versus 1.8 months [0.57 (0.44-0.74), P < 0.0001] in the 4Lþ group. Time to deterioration of ECOG PS to !2 for FTD/TPI versus placebo was 4.8 versus 2.0 months [HR (95% CI) ¼ 0.60 (0.42-0.86), P ¼ 0.0049] in the 3L group; and 4.0 versus 2.5 months [0.75 (0.57-0.98), P ¼ 0.0329] in the 4Lþ group. The safety of FTD/TPI was consistent in all subgroups. Conclusions: This analysis confirms the efficacy and safety of FTD/TPI in patients with GC/EGJ in third and later lines with a survival benefit that seems slightly superior in 3L treatment. When FTD/TPI is taken in 3L as recommended in the international guidelines, physicians can expect to provide patients with an mOS of 6.8 months.

Molecular characterization of colorectal cancer has helped us understand better the biology of the disease. However, previous efforts have yet to provide significant clinical value in order to be integrated into clinical practice for patients with early-stage colon cancer (CC). The purpose of this study was to assess PD-L1, GLUT-1, e-cadherin, MUC2, CDX2, and microsatellite instability (dMMR) and to propose a risk-panel with prognostic capabilities. Biomarkers were immunohistochemically assessed through tissue microarrays in a cohort of 144 patients with stage II/III colon cancer. A biomarker panel consisting of PD-L1, GLUT-1, dMMR, and potentially CDX2 was constructed that divided patients into low, medium, and high risk of overall survival or disease-free survival (DFS) in equally sized groups. Compared with low-risk patients, medium-risk patients have almost twice the risk of death (HR = 2.10 (0.99–4.46), p = 0.054), while high-risk patients have almost four times the risk (HR = 3.79 (1.77–8.11), p = 0.001). The multivariate goodness of fit was 0.756 and was correlated with Kaplan–Meier curves (p = 0.002). Consistent results were found for DFS. This study provides a critical basis for the future development of an immunohistochemical assessment capable of discerning early-stage CC patients as a function of their prognosis. This tool may aid with treatment personalization in daily clinical practice and improve survival outcomes.

229 Background: Metastatic gastroesophageal cancer (GC/GEJC) is an aggressive disease with poor prognosis and a median overall survival (mOS) of around 1 year. While new treatments have emerged, the need for better understanding of the biology and patient profiling is essential given the heterogeneity of the disease. Previously, the TAGS study showed an improved OS with trifluridine/tipiracil (FTD/TPI) vs placebo in heavily pretreated metastatic GC/GEJC patients with a 31% risk reduction in death. This exploratory subgroup analysis of TAGS aims to assess the efficacy, safety, and quality of life (QoL) results observed in patients who received FTD/TPI or placebo in third line (3L) and those who received FTD/TPI beyond the third line (4L+). This analysis will help provide physicians a clearer view of what is expected in the third-line setting in terms of outcomes and to confirm the efficacy of FTD/TPI in later lines. Methods: Patients were divided into two groups: (i) patients who had received FTD/TPI or placebo after two lines of previous systemic therapy (3L) (n = 126 vs 64); and (ii) patients who had received FTD/TPI or placebo (n = 211 vs 106) after three or more lines of previous systemic therapy (4L+). Patient demographics/baseline characteristics, efficacy (OS, progression-free survival [PFS], and time to ECOG deterioration to 2 or more), safety, and QoL were assessed accordingly in these two groups. Results: Patient baseline characteristics in both groups were well balanced between FTD/TPI and placebo. The mOS for FTD/TPI vs placebo in 3L was 6.8 vs 3.2 months (HR, 0.67; 95% CI, 0.47-0.97; P= 0.0318); whereas, in 4L+, it was 5.2 vs 3.7 months (HR, 0.72; 95% CI, 0.55-0.95; P= 0.0192). The mPFS for FTD/TPI vs placebo in 3L was 3.1 vs 1.9 months (HR, 0.54; 95% CI, 0.38-0.77; P= 0.0004); whereas, in 4L+, it was 1.9 vs 1.8 months (HR, 0.57; 95% CI, 0.44-0.74; P< 0.0001). Time to deterioration of ECOG to 2 or more for FTD/TPI vs placebo in 3L was 4.8 vs 2.0 months (HR, 0.60; 95% CI, 0.42-0.86; P= 0.0049); whereas, in 4L+, it was 4.0 vs 2.5 months (HR, 0.75; 95% CI, 0.57-0.98; P= 0.0329). No relevant clinical differences were found in the impact on QoL in the overall study population. The safety profile of FTD/TPI remained consistent through all subgroup analyses. Conclusions: This analysis confirms the efficacy and safety of using FTD/TPI vs placebo in GC/GEJC patients in third and later lines with a survival benefit that seems to be slightly superior in 3L. Results of QoL in both 3L and 4L+ were consistent with previously published subgroup analyses and with the overall TAGS study population. When FTD/TPI is taken in 3L as recommended in the international guidelines, physicians can expect to provide their patients with a mOS of 6.8 and mPFS of 3.1 months. Clinical trial information: NCT02500043.