LBA-002Overall survival results from a phase III trial of trifluridine/tipiracil versus placebo in patients with metastatic gastric cancer refractory to standard therapies (TAGS)

Background: Trifluridine/tipiracil (FTD/TPI), an orally administered combination agent approved for patients with refractory metastatic colorectal cancer, demonstrated promising clinical activity in a refractory gastric cancer Japanese Phase II trial. Therefore, we initiated the TAGS study (NCT02500043) to evaluate the efficacy and safety of FTD/TPI in patients with heavily pretreated metastatic gastric cancer (mGC).

LBA-004Efficacy and safety results from IMblaze370, a randomised Phase III study comparing atezolizumab+cobimetinib and atezolizumab monotherapy vs regorafenib in chemotherapy-refractory metastatic colorectal cancer

Background: Patients with chemotherapy-refractory microsatellite stable (MSS) metastatic colorectal cancer (CRC) are a population with limited treatment options and relatively short survival. Atezolizumab (an anti–PD-L1 mAb) inhibits the binding of PD-L1 to its receptors PD-1 and B7.1, leading to the re-invigoration of tumour-specific T-cell immunity. Cobimetinib inhibits MEK1/MEK2 in the MAPK pathway, and blocking the MAPK pathway has been shown to favourably alter the tumour, tumour microenvironment and T-cell responses to promote anti-tumour immune activity. We hypothesized that combining atezolizumab with cobimetinib may allow better immune recognition and generate greater anti-tumour effects than either agent alone in MSS/microsatellite instability-low (MSI-L) metastatic CRC. Here we report the primary analysis results from IMblaze370 (NCT02788279), a global, multi-centre, open-label, randomised Phase III trial comparing atezolizumab+cobimetinib and atezolizumab monotherapy with standard-of-care regorafenib in patients with previously treated, unresectable locally advanced or metastatic CRC.

LBA-001Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP) following first-line sorafenib: Pooled efficacy and safety across two global randomized Phase 3 studies (REACH-2 and REACH)

Background: Ramucirumab (RAM), a human IgG1 monoclonal antibody, inhibits ligand activation of VEGFR2. REACH and REACH-2 were two global, randomized, double-blind, placebo (PBO)-controlled multicenter, phase 3 studies of RAM vs PBO in patients with HCC after prior sorafenib. REACH-2 was designed to confirm the ramucirumab treatment benefit for patients with baseline AFP ≥400 ng/mL first observed in the prespecified subgroup of patients in REACH with AFP ≥400 ng/mL. The primary endpoint of REACH-2 was met demonstrating an improved overall survival (OS) compared to PBO, a result consistent with that in patients with AFP ≥400 ng/mL in REACH. Pooled analyses of patients from REACH-2 and REACH with baseline AFP ≥400 ng/mL was performed.

LBA-003Withdrawn

LBA-005KEYNOTE-061: Phase 3 study of pembrolizumab vs paclitaxel for previously treated advanced gastric or gastroesophageal junction (G/GEJ) cancer

Background: Pembrolizumab showed promising antitumor activity and a manageable safety profile in patients with pretreated G/GEJ cancer in KEYNOTE-012 and KEYNOTE-059. KEYNOTE-061 (NCT02370498) was a global, open-label phase 3 study of pembrolizumab vs paclitaxel for previously treated advanced G/GEJ adenocarcinoma that progressed after first-line chemotherapy containing platinum and fluoropyrimidine.

Author Index

Abada, Paolo   LBA-001

P-200Risk factors of colorectal cancer in Linxian, China: A nutrition intervention trial with 30 years follow-up

Introduction: Colorectal cancer (CRC) is one of the most common cancers in the world. Epidemiological and experimental studies have shown that some dietary factors and vitamins/minerals are associated with the risk of CRC. The Nutrition Intervention Trial (NIT) tested whether daily multivitamin/mineral supplements could reduce the incidence and mortality rate of esophageal/gastric cardia cancer. The current study evaluated the CRC risk factors at the NIT population.

P-233Trifluridine/tipiracil vs regorafenib as salvage-line treatment in patients with metastatic colorectal cancer: A multicenter retrospective study

Introduction: Trifluridine/tipiracil (TAS-102) and Regorafenib (REG) have shown promising activity in patients with heavily pretreated metastatic colorectal cancer (mCRC). The aim of this study was to compare the efficacy and safety of TAS-102 and REG alone in patients with mCRC refractory to standard chemotherapies.

P-267The prognostic impact of sidedness in RAS wild-type colorectal cancer

Introduction: Colorectal cancer (CRC) is a heterogeneous disease and sidedness [right colon (RC) vs. left colon (LC)] reflects different clinical, biological and molecular behaviors, which could have a significant prognostic impact. This study tried to evaluate the impact of sidedness on overall survival (OS) and progression-free survival (PFS) in RAS wild-type (RAS-WT) CRC patients treated with anti-EGFR antibodies in first line palliative chemotherapy.

PD-008Molecular characterization of immune microenvironment in colorectal cancers with microsatellite instability by digital RNA counting

Introduction: Alterations in the mismatch repair (MMR) mechanism in colorectal cancers (CRCs) lead to high levels of microsatellite instability (MSI-h) causing considerable endogenous immune anti-tumor response, counterbalanced by immune inhibitory signals. We evaluated the mRNA immune-profile of a series of MSI-h CRCs to identify new potential targets for future CRC immunotherapy trials by combining an extensive gene expression analysis and the clinicopathological characteristics such as presence of metastases, staging, genotype and primary tumor sidedness.

P-300Predictive value of circulating tumor-derived DNA (ctDNA) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CT-RT): Preliminary results

Introduction: In patients with LARC, neoadjuvant CT-RT followed by curative surgery is the standard of care. Risk-adopted treatment is based on MRI-predicting local T and N stage, radial margins and vascular involvement while no molecular predictive markers are available. In the present prospective study, we investigated the predictive role of serum ctDNA in patients with LARC.

P-217ABCG2 and TOP-1 as predictive biomarkers and targets for therapy in colon cancer

Introduction: There is a need for new and innovative solutions in the medical treatment of colon cancer since many of these patients eventually develop resistance to currently used drugs leading to untreatable cancer disease and death of the patients. We have by using our DEN50-R cell line based screening platform (isogenic pairs of drug sensitive and drug resistant human cancer cell lines), followed by testing in the PETACC-3 prospective randomized clinical study, identified ABCG2 and TOP1 mRNA expression as significant predictive biomarkers for irinotecan (a topoisomerase 1 inhibitor) resistance in the adjuvant treatment of colon cancer. Moreover, we have identified a new drug (SCO-101) that reverses irinotecan resistance in preclinical experiments (the DEN50-R platform). Here we present the clinical data with the biomarkers and data on SCO-101 including the clinical development plans for the drug.

P-251The prognostic ad predictive value of primary tumor sidedness in the mCRC pts

Introduction: The prognostic and predictive value of primary tumor sidedness in the pts with metastatic colorectal cancer (mCRC) is well known today. Right-sided primary was associated with high mutational burden, microsatellite instability, worse prognosis, more BRAF mutation rates and poor anti-EGFR response. We aimed to investigate the effects of tumor sidedness on survival, RAS-RAF mutation rates and responses to biologic agents in the pts with mCRC.

P-284Characteristics of colorectal cancer in the elderly patients about 60 cases

Introduction: Older people constitute a heterogeneous population, according to World Health Organization, the elderly person is defined as any individual with a chronological age equal to or higher than 60 years. In most cases, colorectal carcinoma is a disease of the elderly. Occurs mostly in the elderly people of more than 65 years and it poses public health problem. For several years geriatric evaluation has shown multiple benefits and we are witnessing a significant improvement in the oncological management of these patients.

P-316Is there any association of dose received by pelvic bone marrow in preoperative radiotherapy in rectal cancer with hematological toxicity of subsequent oxaliplatin-based chemotherapy?

Introduction: Preoperative radio(chemo)therapy in rectal cancer may irreversibly damage pelvic bone marrow (PBM) and impair the tolerance of subsequent chemotherapy. The aim of the study was to assess the association between irradiated volume of PBM and the tolerance of subsequent FOLFOX-4 chemotherapy in rectal cancer.

WITHDRAWN

O-001Efficacy of TAS-120, an irreversible fibroblast growth factor receptor (FGFR) inhibitor, in cholangiocarcinoma patients with FGFR pathway alterations who were previously treated with chemotherapy and other FGFR inhibitors

Introduction: TAS-120, an oral and highly selective, irreversible FGFR1-4 tyrosine kinase inhibitor, has demonstrated inhibition of cancer cell growth in human xenografts of tumors bearing FGFR aberrations. TAS-120 inhibited mutant and wild-type FGFR2 with similar IC50 (wild-type FGFR2, 0.9 nM; V5651, 1-3 nM; N550H, 3.6 nM; E566G, 2.4 nM) and has shown efficacy in cell lines with acquired resistance to FGFR inhibitors. In this Phase I study in patients with advanced solid tumors, TAS-120 was evaluated at 8-24 mg once daily (QD). 20 mg QD was determined as the maximum tolerated dose/recommended Phase II dose, while 24 mg QD had dose-limiting toxicity. Here we report results from cholangiocarcinoma (CCA) patients enrolled in this Phase I study.

P-191Combined analysis of KRAS, NRAS, BRAF mutations and mismatch repair deficiency testing in Indian patients with metastatic colorectal carcinoma: A single centre experience

Introduction: Molecular evaluation of KRAS, NRAS and BRAF mutation has become an important part in colorectal carcinoma evaluation as their alterations determine the therapeutic response to anti-EGFR therapy and prognosis. MMR deficiency is important for identification of Lynch syndrome families and it has now become an important biomarker of response to immunotherapy in metastatic CRC. The aim of this study is to investigate the distribution of these mutations by tumor localization and to determine the prevalence of MMR deficiency in metastatic colorectal cancer.

P-208Autophagy (A) related proteins evaluation represents an independent survival factor of colorectal cancer (CRC) patients (pts)

Introduction: A holds a bimodal role during carcinogenesis. Before tumorigenesis, A promotes normal cells survival and suppress carcinogenesis, while after cancer development A induces cancer cells survival. The aim of this study is to assess the impact of A related proteins in the survival of CRC pts.

P-225The role of maintenance therapy in the first line treatment of metastatic colorectal cancer

Introduction: The first line of chemotherapy is decisive in the treatment of colorectal cancer. Choosing the right one allows you to increase PFS and improve long-term results. Surgical treatment and maintenance therapy (MT) increase PFS and OS, as they can be prescribed at any stage of treatment.