ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Updated Efficacy Outcomes of Anti-PD-1 Antibodies plus Multikinase Inhibitors for Patients with Advanced Gastric Cancer with or without Liver Metastases in Clinical Trials.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Sintilimab plus fruquintinib with or without radiotherapy for third-line treatment of colorectal cancer with liver metastases: study protocol for a randomized controlled, multicenter phase II trial.Frontiers in immunology · 2026Trial
- Trial
- Spatial immune niches in gastric cancer immunotherapy resistance: mechanisms and translational implications.Frontiers in immunology · 2026Review
- Exploration of the benefits and resistance mechanisms of immunotherapy based on PD-L1 expression, circulating tumor DNA and T-cell receptor profiles in advanced gastric cancer.Cancer immunology, immunotherapy : CII · 2025Article
- Convergent systemic therapy for liver metastases: Bridging primary tumor heterogeneity through shared pathways.iLIVER · 2025Review
- Article
- Lenvatinib suppress FGF19-FGFR4 signaling to enhance antitumor immune response in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Regulatory T cells in liver metastases: emerging and divergent roles in tumour progression.eGastroenterology · 2025Review
- Real-World Efficacy of Cadonilimab Plus Chemotherapy as Second-Line Therapy in Immunotherapy-Pretreated Advanced HER2 Negative Gastric or Gastroesophageal Junction Cancer.Drug design, development and therapy · 2025Article
- Nanomaterials for liver cancer targeting: research progress and future prospects.Frontiers in immunology · 2025Review
- Immunosuppressive tumor microenvironment in gastric signet-ring cell carcinoma.World journal of clinical oncology · 2024Article
- Antiangiogenic-immune-checkpoint inhibitor combinations: lessons from phase III clinical trials.Nature reviews. Clinical oncology · 2024Review
- Organ-specific response with first-line atezolizumab-bevacizumab versus lenvatinib for patients with advanced hepatocellular carcinoma.Hepatology international · 2024Article
- New clinical trial design in precision medicine: discovery, development and direction.Signal transduction and targeted therapy · 2024Review
- A multicenter retrospective study of the combination of immune checkpoint inhibitors and chemotherapy regimens with or without liver metastasis for the first-line treatment of advanced gastric cancer.Therapeutic advances in medical oncology · 2024Article
- Site of distant metastasis affects the prognosis with recurrent/metastatic head and neck squamous cell carcinoma patients treated with Nivolumab.International journal of clinical oncology · 2023Review
- Mesoporous Nanoparticles for Diagnosis and Treatment of Liver Cancer in the Era of Precise Medicine.Pharmaceutics · 2022Review
- Integrated analysis of necroptosis-related genes for evaluating immune infiltration and colon cancer prognosis.Frontiers in immunology · 2022Article
- Prognostic characteristics and clinical response to immunotherapy targeting programmed cell death 1 for patients with advanced gastric cancer with liver metastases.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
23 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeWe previously reported preliminary activity of regorafenib plus nivolumab (REGONIVO) or lenvatinib plus pembrolizumab (LENPEM) in advanced gastric cancer (AGC). Meanwhile, several studies demonstrated liver metastases are less responsive to immunotherapy. PATIENTS AND
methodsCombined efficacy outcomes with a longer follow-up in a phase Ib trial of REGONIVO and a phase II trial of LENPEM were examined in AGC with or without liver metastases (REGONIVO plus LENPEM cohort). We also investigated the efficacy of anti-PD-1 monotherapies (anti-PD-1 monotherapy cohort). A comparison of the immune microenvironment between gastric primary tumors and liver metastases was also conducted by multiplex IHC.
resultsIn the REGONIVO plus LENPEM cohort, with a median follow-up of 14.0 months, objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) were 46%, 7.8 months, and 15.6 months in patients with liver metastases, while 69%, 6.9 months, and 15.5 months in those without. In the anti-PD-1 monotherapy cohort, with a median follow-up of 27.6 months, ORR, mPFS, and mOS were 9%, 1.4 months, and 6.4 months in patients with liver metastases, while 22%, 2.3 months, and 9.0 months in those without. Multiplex IHC revealed liver metastases were associated with an abundance of immune-suppressive cells, such as tumor-associated macrophages and regulatory T cells, with fewer CD8+ T cells compared with gastric primary tumors.
conclusionsAnti-PD-1 antibodies plus regorafenib or lenvatinib for AGC showed promising antitumor activity with a longer follow-up, irrespective of liver metastases status, despite a more immune-suppressive tumor microenvironment in liver metastases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.