Impact of multidisciplinary team intervention on long-term survival in distant metastatic colorectal cancer: Single-centre propensity score analyses.

Aim: Multidisciplinary team (MDT) intervention is generally recommended in patients with distant metastatic colorectal cancer (DMCRC). However, it is not clear whether MDT intervention has a favourable impact on prognosis. We investigated the impact of MDT intervention on improving long-term prognosis in DMCRC.

Ramucirumab-containing chemotherapy for patients with gastrointestinal neuroendocrine carcinoma refractory/intolerant to platinum-based chemotherapy: A multicenter observational retrospective study (WJOG13420G).

No standard second-line chemotherapy has been established for gastrointestinal neuroendocrine carcinoma (NEC). This study aimed to determine whether ramucirumab (RAM) is a treatment candidate in this setting. We retrospectively collected data from patients with gastric and colorectal NEC who received second-line chemotherapy following platinum-based chemotherapy.

Epidemiologic Features and Age-Related Differences in Management among Patients with Gastrointestinal Stromal Tumors in Japan: A National Cancer Registry Study.

Unlabelled: Data on the epidemiology of gastrointestinal stromal tumor (GIST) and differences in its management according to age group are limited in Japan. We aimed to conduct an epidemiologic evaluation and describe age-related differences in management using data from Japan's National Cancer Registry. We analyzed National Cancer Registry data of 21,426 patients with GIST between 2016 and 2019.

Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment of advanced gastric or gastroesophageal junction adenocarcinoma: patient-reported outcomes in the RATIONALE-305 study.

Objective: RATIONALE-305 (NCT03777657) demonstrated that tislelizumab plus chemotherapy statistically improved overall survival versus placebo plus chemotherapy as first-line treatment in patients with advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC). This analysis examined patient-reported outcomes (PROs) at final analysis.

Methods: Adults with previously untreated, unresectable, or metastatic GC/GEJC were randomized (1:1) to tislelizumab or placebo intravenously once every 3 weeks plus chemotherapy.

A multicenter Phase II study of mFOLFOX6 plus nivolumab for gastric cancer with severe peritoneal metastases: WJOG16322G.

Advanced gastric cancer (AGC) patients with severe peritoneal metastases (SPM), characterized by massive ascites and/or inadequate oral intake, have a poor prognosis with the median overall survival of around 7 months, even when treated with fluorouracil/l-leucovorin plus oxaliplatin (mFOLFOX6), despite being a treatment options for these patients demonstrated in the WJOG10517G study. However, these patients were excluded from pivotal Phase III trials, including the CheckMate 649 study, which demonstrated the benefit of adding nivolumab to mFOLFOX6, due to tumor-related complications. Given the lack of data on the efficacy and safety of combining nivolumab with mFOLFOX6 for AGC patients with SPM, we initiated a Phase II study to evaluate this combination.

Phase II Study (NO LIMIT, WJOG13320G) of First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High Advanced Gastric or Esophagogastric Junction Cancer.

Purpose: Microsatellite instability-high (MSI-H) advanced gastric or esophagogastric junction cancer (AGC), accounting for 5%-6% of all AGC cases, has shown an enhanced responsiveness to immunotherapy. We performed a single-arm phase II study to evaluate the combination of nivolumab (NIVO) and low-dose (LD) ipilimumab (IPI) for first-line treatment of MSI-H AGC.

Patients And Methods: Patients with MSI-H AGC received NIVO (240 mg once every 2 weeks) and IPI (1 mg/kg once every 6 weeks).

First-Line Tislelizumab Plus Chemotherapy for Advanced Gastric Cancer with Programmed Death-Ligand 1 Expression ≥ 1%: A Retrospective Analysis of RATIONALE-305.

Introduction: Tislelizumab plus investigator-chosen chemotherapy (ICC) demonstrated a statistically significant improvement in overall survival (OS) versus placebo plus ICC in RATIONALE-305 in patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric cancer/gastroesophageal junction cancer (GC/GEJC) in the intent-to-treat population and in patients with programmed death-ligand 1 (PD-L1) Tumor Area Positivity (TAP) score ≥ 5%. The United States Food and Drug Administration Oncologic Drugs Advisory Committee voted (September 2024) against first-line treatment with programmed cell death protein-1 inhibitors in this setting in patients with a PD-L1 combined positive score < 1 or TAP score < 1%, due to an unfavorable benefit-risk profile. Thus, we retrospectively analyzed data from RATIONALE-305 in patients with a PD-L1 TAP score ≥ 1%.

Phase 2 study of futibatinib in patients with gastric or gastroesophageal junction cancer harboring FGFR2 amplifications.

Background And Aims: Aberrant fibroblast growth factor receptor (FGFR)-driven signaling, predominantly arising from FGFR2 amplification, plays a key role in gastric cancer pathogenesis. This open-label, phase 2 study evaluated the efficacy and safety of futibatinib, an irreversible FGFR1-4 inhibitor, in patients with gastric or gastroesophageal junction (GEJ) cancer harboring FGFR2 amplifications.

Methods: Patients were treated with futibatinib 20 mg orally once daily in a 28-day cycle.

Phase II trial of nab-paclitaxel plus ramucirumab in combination with nivolumab for unresectable advanced or recurrent gastric cancer after progression on first-line treatment including fluoropyrimidine, platinum, and anti-PD-1/PD-L1 antibody (PADDLE).

Background: Patients with advanced gastric cancer (AGC) have poor survival after first-line treatment containing an anti-programmed death-1/ligand 1 (PD-1/PD-L1) antibody. Accumulating evidence suggests rationales for continuing immunotherapy beyond progression, synergistic effects between immune checkpoint inhibitors and angiogenesis inhibitors, and a preferable combination of steroid-free chemotherapy with immunotherapy. These rationales imply that nanoparticle albumin-bound (nab)-paclitaxel plus ramucirumab in combination with nivolumab (anti-PD-1 antibody) may enhance anti-tumor effects as second-line treatment.

Clinicopathological and molecular features of claudin-18 isoform 2 expression in patients with colorectal cancer: a single-center retrospective study.

Background: Claudin-18 isoform 2 (CLDN18.2) is expressed in multiple cancers and is a promising target for antitumor therapy. However, there is limited knowledge regarding the prevalence and characteristics of CLDN18.

Sex differences in toxicities and survival outcomes among Japanese patients with Stage III colorectal cancer receiving adjuvant fluoropyrimidine monotherapy: A pooled analysis of 4 randomized controlled trials (JCOG2310A).

Background: Fluoropyrimidine remains the key agent of adjuvant chemotherapy for stage III colorectal cancer (CRC). Western studies have shown that female sex is a favorable prognostic factor after surgery, but it is also a risk factor for adverse events (AEs) during adjuvant chemotherapy with fluoropyrimidine. However, little is known about whether sex differences in treatment outcomes exist in this setting in the Asian population.

Predictive and prognostic value of excision repair cross-complementing group 1 in patients with advanced gastric cancer.

Background: To define the optimal chemotherapy regimen for each patient we therefore used tissue from patients to identify molecular prognostic or predictive biomarkers.

Methods: Endoscopic biopsy specimens from primary lesions and surgical specimens on a phase III trial in patients with unresectable advanced or recurrent gastric cancer treated with docetaxel with cisplatin plus S-1 (DCS) or cisplatin plus S-1 (CS), were collected. We measured the mRNA expression of ERCC1 and analyzed SNPs in GSTP1 and ERCC1.

Different efficacy of tyrosine kinase inhibitors by KIT and PGFRA mutations identified in circulating tumor DNA for the treatment of refractory gastrointestinal stromal tumors.

Background: While advanced gastrointestinal stromal tumors (GISTs) are primarily treated with tyrosine kinase inhibitors (TKIs), acquired resistance from specific mutations in KIT or PDGFRA frequently occurs. We aimed to assess the utility of circulating tumor DNA (ctDNA) as a modality of therapeutic decision-making in advanced GIST.

Methods: We conducted a pooled analysis of SCRUM-Japan studies for advanced GIST patients.

Comprehensive Genomic Assessment of Advanced-Stage GI Stromal Tumors Using the Japanese National Center for Cancer Genomics and Advanced Therapeutics Database.

Purpose: Clinical utility of comprehensive genomic profiling (CGP) for precision medicine has become evident. Although there are several reports on the genomic landscape of GI stromal tumors (GISTs), large-scale data specific to GIST are limited, especially in Asia. Additionally, the applicability of molecular-targeted agents identified using CGP has not been extensively examined.

Targeting SNCA in the treatment of malignant ascites in gastrointestinal cancer.

Peritoneal tumor dissemination and subsequent malignant tumor ascites (MTA) occur unexpectedly and repeatedly in patients with gastrointestinal (GI) cancers, and worsen quality of life and prognosis of the patients. Various treatments have been clinically developed for these patients, while most of the MTA cases are refractory to the treatments. Thus, effective treatments are urgently needed to improve the clinical outcomes.

Efficacy of anti-epidermal growth factor antibody rechallenge in RAS/BRAF wild-type metastatic colorectal cancer: a multi-institutional observational study.

Purpose: To investigate circulating tumor DNA (ctDNA) RAS mutant (MT) incidence before salvage-line treatment and the clinicopathological features and molecular biological factors associated with the efficacy of anti-epithelial growth factor receptor (EGFR) monoclonal antibody (mAb) rechallenge for tissue RAS/BRAF wild type (WT) metastatic colorectal cancer (mCRC).

Methods: This multi-institutional retrospective observational study included 74 patients with mCRC with tissue RAS/BRAF WT refractory to first-line chemotherapy containing anti-EGFR mAb. ctDNA RAS status was assessed using the OncoBEAM™ RAS CRC Kit.

Impact of immune checkpoint inhibitors on survival outcomes in advanced gastric cancer in Japan: A real-world analysis.

Background: Nivolumab was approved for the treatment of advanced gastric cancer in 2017 in Japan. The aim of this study was to assess the impact of nivolumab in a real-world clinical setting.

Methods: This single-institutional retrospective study included patients with advanced gastric or esophagogastric junction adenocarcinoma and a history of first-line chemotherapy with platinum-based doublet or triplet regimens between 2010 and 2020.

V600E-mutant colorectal cancer with CNS metastases treated successfully with encorafenib, binimetinib and cetuximab.

This report describes a case of BRAF V600E-mutated colorectal cancer with CNS metastases in which treatment with encorafenib, binimetinib and cetuximab was effective. There is limited information on the ability of encorafenib, binimetinib and cetuximab to enter the CNS.The patient was a 53-year-old man was diagnosed with ascending colon cancer (cT3N3M1c stage IVc).

CRP and soluble CTLA4 are determinants of anti-PD1 resistance in gastrointestinal cancer.

Targeting immune inhibitory checkpoint (IC) pathways have attracted great attention as a promising strategy for treating gastrointestinal (GI) cancer. However, the therapeutic efficacy is low in most cases, and little progress has been made in establishing biomarkers that predict the possible responses, and combination regimens that enhance the therapeutic efficacy. As a predictive biomarker, soluble forms of IC molecules have been recently highlighted.

Exploratory analysis of serum HER2 extracellular domain for HER2 positive gastric cancer treated with SOX plus trastuzumab.

Background: The aim of this study was to explore the clinical utility of serum HER2 extracellular domain (sHER2 ECD) using data from a clinical trial evaluating trastuzumab combined S-1 plus oxaliplatin (SOX) in HER2 positive gastric cancer.

Methods: sHER2 ECD were prospectively measured at baseline and subsequent treatment courses. Based on each quantile point of baseline sHER2 ECD levels and its early changes, patients were divided into two groups and compared clinical outcomes.