Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial

China is one of the countries with the highest incidence of gastric cancer. There are differences in epidemiological characteristics, clinicopathological features, tumor biological characteristics, treatment patterns, and drug selection between gastric cancer patients from the Eastern and Western countries. Non-Chinese guidelines cannot specifically reflect the diagnosis and treatment characteristics for the Chinese gastric cancer patients. The Chinese Society of Clinical Oncology (CSCO) arranged for a panel of senior experts specializing in all sub-specialties of gastric cancer to compile, discuss, and revise the guidelines on the diagnosis and treatment of gastric cancer based on the findings of evidence-based medicine in China and abroad. By referring to the opinions of industry experts, taking into account of regional differences, giving full consideration to the accessibility of diagnosis and treatment resources, these experts have conducted experts’ consensus judgement on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes. This guideline uses tables and is complemented by explanatory and descriptive notes covering the diagnosis, comprehensive treatment, and follow-up visits for gastric cancer.

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The Chinese Society of Clinical Oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer.

Purpose: This study assessed the safety and efficacy of SHR-1210 (anti-PD-1 antibody) and apatinib (VEGFR2 inhibitor) as combination therapy in patients with advanced hepatocellular carcinoma (HCC), gastric, or esophagogastric junction cancer (GC/EGJC). Patients and Methods: This was an open-label, dose-escalation (phase Ia) and expansion study (phase Ib). In phase Ia, patients (n = 15) received SHR-1210 200 mg every 2 weeks and apatinib 125–500 mg once daily until unacceptable toxicity or disease progression. In phase Ib, patients (n = 28) received apatinib at the phase Ia–identified recommended phase II dose (RP2D) plus SHR-1210. The primary objectives were safety and tolerability and RP2D determination. Results: At data cutoff, 43 patients were enrolled. In phase Ia, four dose-limiting toxicity events were observed (26.7%): one grade 3 lipase elevation (6.7%) in the apatinib 250 mg cohort and three grade 3 pneumonitis events (20%) in the apatinib 500 mg cohort. The maximum tolerated RP2D for apatinib was 250 mg. Of the 33 patients treated with the R2PD combination, 20 (60.6%) experienced a grade ≥3 treatment-related adverse event; adverse events in ≥10% of patients were hypertension (15.2%) and increased aspartate aminotransferase (15.2%). The objective response rate in 39 evaluable patients was 30.8% (95% CI: 17.0%–47.6%). Eight of 16 evaluable HCC patients achieved a partial response (50.0%, 95% CI: 24.7%–75.4%). Conclusions: SHR-1210 and apatinib combination therapy demonstrated manageable toxicity in patients with HCC and GC/EGJC at recommended single-agent doses of both drugs. The RP2D for apatinib as combination therapy was 250 mg, which showed encouraging clinical activity in patients with advanced HCC.

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Anti-PD-1 Antibody SHR-1210 Combined with Apatinib for Advanced Hepatocellular Carcinoma, Gastric, or Esophagogastric Junction Cancer: An Open-label, Dose Escalation and Expansion Study.

Summary Background Trifluridine/tipiracil showed activity and was well tolerated in a phase 2 study of pretreated patients with advanced gastric cancer done in Japan. We investigated whether the treatment was efficacious compared with placebo in a global population. Methods TAGS was a randomised, double-blind, placebo-controlled, phase 3 trial done in 110 academic hospitals in 17 countries. Patients aged 18 years or older with histologically confirmed, non-resectable, metastatic gastric adenocarcinoma (including adenocarcinoma of the gastroesophageal junction) as defined by the American Joint Committee on Cancer staging classification (7th edition) who had received at least two previous chemotherapy regimens and had experienced radiological disease progression were eligible for inclusion. Patients were randomly assigned (2:1) via dynamic randomisation from a centralised interactive voice-response system to receive either oral trifluridine/tipiracil (35 mg/m2 twice daily on days 1–5 and days 8–12 every 28 days) plus best supportive care or placebo plus best supportive care. Participants were allocated to groups by study-site personnel. Randomisation was stratified by region (Japan vs rest of world), ECOG performance status (0 vs 1), and previous treatment with ramucirumab (yes vs no). Both patients and investigators were masked to treatment allocation. The primary endpoint was overall survival. Efficacy was assessed in the intention-to-treat population and safety in all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov , number NCT02500043 . The trial, including follow-up of all participants, has been completed. Findings Between Feb 24, 2016, and Jan 5, 2018, 507 patients were enrolled and randomly assigned, 337 to the trifluridine/tipiracil group and 170 to the placebo group. Median overall survival was 5·7 months (95% CI 4·8–6·2) in the trifluridine/tipiracil group and 3·6 months (3·1–4·1) in the placebo group (hazard ratio 0·69 [95% CI 0·56–0·85]; one-sided p=0·00029, two-sided p=0·00058). Grade 3 or worse adverse events of any cause occurred in 267 (80%) patients in the trifluridine/tipiracil group and 97 (58%) in the placebo group. The most frequent grade 3 or worse adverse events of any cause were neutropenia (n=114 [34%]) and anaemia (n=64 [19%]) in the trifluridine/tipiracil group and abdominal pain (n=15 [9%]) and general deterioration of physical health (n=15 [9%]) in the placebo group. Serious adverse events of any cause were reported in 143 (43%) patients in the trifluridine/tipiracil group and 70 (42%) in the placebo group. One treatment-related death was reported in each group (because of cardiopulmonary arrest in the trifluridine/tipiracil group and because of toxic hepatitis in the placebo group). Interpretation Trifluridine/tipiracil significantly improved overall survival compared with placebo and was well tolerated in this heavily pretreated population of patients with advanced gastric cancer. Trifluridine/tipiracil could be a new treatment option in this population who represent a high unmet medical need. Funding Taiho Oncology and Taiho Pharmaceutical.

Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic oesophageal cancer: a JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS.

PurposeThere is currently no standard treatment strategy for patients with advanced metastatic gastric cancer experiencing progression after two or more lines of chemotherapy. We assessed the efficacy and safety of apatinib, a novel vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, in patients with advanced gastric or gastroesophageal junction adenocarcinoma for whom at least two lines of prior chemotherapy had failed.Patients and MethodsThis was a randomized, double-blind, placebo-controlled phase III trial. Patients from 32 centers in China with advanced gastric or gastroesophageal junction adenocarcinoma, for whom two or more prior lines of chemotherapy had failed, were enrolled. Patients were randomly assigned to oral apatinib 850 mg or placebo once daily. The primary end points were overall (OS) and progression-free survival (PFS).ResultsBetween January 2011 and November 2012, 267 patients were enrolled. Median OS was significantly improved in the apatinib group compared with t...

Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction

Piaoyang Sun

Papers

Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction

Discovery and reduction of tryptophan oxidation-induced IgG1 fragmentation in a polysorbate 80-dependent manner.