Recent Advances in Immunotherapy and Molecular Targeted Therapy for Gastric Cancer

References

• HyunaS , JacquesF , RebeccaLet al.Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. A Cancer Journal for Clinicians71, 209–249 (2021).
   PubMed Web of Science ®Google Scholar
• SuzanneL , StephenHodi F , JulieRet al.Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med.366(26), 2443–2454 (2012).
   PubMed Web of Science ®Google Scholar
• CarolineR , GeorginaV , BenjaminBet al.Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med.372(4), 320–330 (2015).
   PubMed Web of Science ®Google Scholar
• AurelienM , DungTL , PaoloAet al.Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the phase II KEYNOTE-158 Study. J. Clin. Oncol.38(1), 1–10 (2020).
   PubMed Web of Science ®Google Scholar
• Yoon-KooK , NarikazuB , TarohSet al.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. Lancet390(10111), 2461–2471 (2017).
   PubMed Web of Science ®Google Scholar
• YelenaYJ , KoheiS , MarkusMet al.First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet398(10294), 27–40 (2021).
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature513(7517), 202–209 (2014).
   PubMed Web of Science ®Google Scholar
• GwenM , RuthP , ConstanzaMCet al.Meta-analysis shows that prevalence of Epstein–Barr virus-positive gastric cancer differs based on sex and anatomic location. Gastroenterology137(3), 824–833 (2009).
   PubMed Web of Science ®Google Scholar
• SeungTK , RazvanC , AdamJBet al.Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat. Med.24(9), 1449–1458 (2018).
   PubMed Web of Science ®Google Scholar
• AnshumanP , JaniceMM , KimMHet al.Immune Activation and Benefit From Avelumab in EBV-Positive Gastric Cancer. J. Natl Cancer Inst.110(3), 316–320 (2018).
   PubMedGoogle Scholar
• WangF , WeiXL , WangFHet al.Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD-1 antibody in phase Ib/II clinical trial NCT02915432. Ann. Oncol.30(9), 1479–1486 (2019).
   PubMed Web of Science ®Google Scholar
• NicolasJL , MichaelC , AdaTet al.The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov.5(1), 43–51 (2015).
   PubMed Web of Science ®Google Scholar
• DungTL , JenniferND , KellieNSet al.Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science357(6349), 409–413 (2017).
   PubMed Web of Science ®Google Scholar
• AkihitoK , KoheiS , YasutoshiKet al.Clinicopathological features of 22C3 PD-L1 expression with mismatch repair, Epstein–Barr virus status, and cancer genome alterations in metastatic gastric cancer. Gastric Cancer22(1), 69–76 (2019).
   PubMed Web of Science ®Google Scholar
• YoheiK , AkihitoK , AkinoriSet al.The Impact of Molecular Subtype on Efficacy of Chemotherapy and Checkpoint Inhibition in Advanced Gastric Cancer. Clin. Cancer Res.26(14), 3784–3790 (2020).
   PubMed Web of Science ®Google Scholar
• KoheiS , MustafaÖ , Yung-JueBet al.Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet392(10142), 123–133 (2018).
   PubMed Web of Science ®Google Scholar
• CharlesSF , ToshihikoD , RaymondWJet al.Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncol.4(5), e180013 (2018).
   PubMed Web of Science ®Google Scholar
• KoheiS , EricVC , Yung-JueBet al.Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 phase 3 Randomized Clinical Trial. JAMA Oncol.6(10), 1571–1580 (2020).
   PubMed Web of Science ®Google Scholar
• MarkusM , MikhailD , NarikazuBet al.Phase III Trial of Avelumab Maintenance After First-Line Induction Chemotherapy Versus Continuation of Chemotherapy in Patients With Gastric Cancers: Results From JAVELIN Gastric 100. J. Clin. Oncol.39(9), 966–977 (2021).
   PubMed Web of Science ®Google Scholar
• KoheiS , JafferAA , MarkusMet al.Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature603(7903), 942–948 (2022).
   PubMed Web of Science ®Google Scholar
• SylvieL , Thuss-PatiencePC , JorgeRKet al.FOLFOX plus nivolumab and ipilimumab versus FOLFOX induction followed by nivolumab and ipilimumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction: results from the randomized phase II Moonlight trial of the AIO. Ann. Oncol.33(Suppl. 7), S555–S580 (2022).
   Web of Science ®Google Scholar
• Yoon-KooK , Li-TzongC , Min-HeeRet al.Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol.23(2), 234–247 (2022).
   PubMed Web of Science ®Google Scholar
• SakuraI , AtsuoT , KentaroSet al.Survival impact of post-progression chemotherapy in advanced gastric cancer: systematic review and meta-analysis. Cancer Chemother. Pharmacol.81(6), 981–989 (2018).
   PubMed Web of Science ®Google Scholar
• HansjochenW , KeiM , EricVCet al.Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol.15(11), 1224–1235 (2014).
   PubMed Web of Science ®Google Scholar
• XuJ , JiangH , PanYet al.Sintilimab plus chemotherapy (chemo) versus chemo as first-line treatment for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (ORIENT-16): first results of a randomized, double-blind, phase III study. Ann. Oncol.32, S1331 (2021).
   Web of Science ®Google Scholar
• SunYR , LucjanSW , PatricioYWet al.Pembrolizumab (pembro) plus chemotherapy (chemo) as first-line therapy for advanced HER2-negative gastric or gastroesophageal junction (G/GEJ) cancer: phase III KEYNOTE-859 study. ESMO Virtual Plenary34(3), P319–P320 (2023).
   Google Scholar
• MarkusM , KenK , TobiasAet al.RATIONALE-305: phase 3 Study of Tislelizumab+Chemotherapy vs Placebo+Chemotherapy as First-line Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma. Journal of Clinical Oncology.41(Suppl.4) 286 (2023).
   Google Scholar
• CharlesSF , MustafaÖ , Yung-JueBet al.Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial. Gastric Cancer25(1), 197–206 (2022).
   PubMed Web of Science ®Google Scholar
• BangYJ , RuizEY , Van CutsemEet al.Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann. Oncol.29(10), 2052–2060 (2018).
   PubMed Web of Science ®Google Scholar
• PeterS , JavierC , LajosPet al.Pembrolizumab for Early Triple-Negative Breast Cancer. N. Engl. J. Med.382(9), 810–821 (2020).
   PubMed Web of Science ®Google Scholar
• CatherineAS , JustinFG , MarkMAet al.Neoadjuvant atezolizumab and chemotherapy in patients with resectable non-small-cell lung cancer: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol.21(6), 786–795 (2020).
   PubMed Web of Science ®Google Scholar
• AlexanderCH , RobertJO , XiaoweiXet al.A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma. Nat. Med.25(3), 454–461 (2019).
   PubMed Web of Science ®Google Scholar
• RavindraU , KatieMC , AnnMEet al.Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, phase II Trial. Clin. Cancer Res.26(19), 5140–5152 (2020).
   PubMed Web of Science ®Google Scholar
• ThierryA , DavidT , GuillaumePet al.Neoadjuvant Nivolumab Plus Ipilimumab and Adjuvant Nivolumab in Localized Deficient Mismatch Repair/Microsatellite Instability-High Gastric or Esophagogastric Junction Adenocarcinoma: The GERCOR NEONIPIGA Phase II Study. J. Clin. Oncol.41(2), 255–265 (2022).
   PubMed Web of Science ®Google Scholar
• Yung-JueB , EricVC , CharlesSFet al.KEYNOTE-585: phase III study of perioperative chemotherapy with or without pembrolizumab for gastric cancer. Future Oncol.15(9), 943–952 (2019).
   PubMed Web of Science ®Google Scholar
• YelenaYJ , EricVC , KeiMet al.MATTERHORN: phase III study of durvalumab plus FLOT chemotherapy in resectable gastric/gastroesophageal junction cancer. Future Oncol.18(20), 2465–2473 (2022).
   Web of Science ®Google Scholar
• KiwamuA , EijiO , HiroyaTet al.The real-world data on microsatellite instability status in various unresectable or metastatic solid tumors. Cancer Sci.112(3), 1105–1113 (2021).
   PubMed Web of Science ®Google Scholar
• AurelienM , DungTL , PaoloAAet al.Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the phase II KEYNOTE-158 Study. J. Clin. Oncol.38(1), 1–10 (2020).
   PubMed Web of Science ®Google Scholar
• JosephC , CharlesSF , KoheiSet al.Assessment of Pembrolizumab Therapy for the Treatment of Microsatellite Instability-High Gastric or Gastroesophageal Junction Cancer Among Patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Clinical Trials. JAMA Oncol.7(6), 895–902 (2021).
   PubMed Web of Science ®Google Scholar
• HisatoK , ShuichiH , TaitoEet al.An Investigator-Initiated phase 2 Study of Nivolumab Plus Low-Dose Ipilimumab as First-Line Therapy for Microsatellite Instability-High Advanced Gastric or Esophagogastric Junction Cancer (NO LIMIT, WJOG13320G/CA209-7W7). Cancers (Basel)13(4), 805 (2021).
   PubMed Web of Science ®Google Scholar
• ZacharyRC , CaitlinFC , DavidFet al.Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med.9(1), 34 (2017).
   PubMedGoogle Scholar
• AparnaRP , YutingH , TedSHet al.Analysis of DNA Damage Response Gene Alterations and Tumor Mutational Burden Across 17,486 Tubular Gastrointestinal Carcinomas: Implications for Therapy. Oncologist24(10), 1340–1347 (2019).
   PubMed Web of Science ®Google Scholar
• FooteMB , MaronSB , CercekAet al.TMB cut-offs fail to predict benefit of PD-1 blockade in gastroesophageal adenocarcinoma in KEYNOTE-061. Ann. Oncol.32(9), 1188–1189 (2021).
   PubMed Web of Science ®Google Scholar
• RituparnaD , RakeshV , MarioSet al.Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo. J. Immunol.194(3), 950–959 (2015).
   PubMed Web of Science ®Google Scholar
• DennisD , SabineH , SusanneKet al.Regorafenib enhances anti-PD1 immunotherapy efficacy in murine colorectal cancers and their combination prevents tumor regrowth. J. Exp. Clin. Cancer Res.40(1), 288 (2021).
   PubMed Web of Science ®Google Scholar
• Da-LiangO , Chia-WeiC , Chia-LangHet al.Regorafenib enhances antitumor immunity via inhibition of p38 kinase/Creb1/Klf4 axis in tumor-associated macrophages. J. Immunother. Cancer9(3), e001657 (2021).
   PubMed Web of Science ®Google Scholar
• YuK , KimiyoT , TakayukiKet al.Lenvatinib plus anti-PD-1 antibody combination treatment activates CD8+ T cells through reduction of tumor-associated macrophage and activation of the interferon pathway. PLOS ONE14(2), e0212513 (2019).
   PubMed Web of Science ®Google Scholar
• ShotaF , HirokiH , NaokiTet al.Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603). J. Clin. Oncol.38(18), 2053–2061 (2020).
   PubMed Web of Science ®Google Scholar
• AkihitoK , ShotaF , YoshiakiNet al.Lenvatinib plus pembrolizumab in patients with advanced gastric cancer in the first-line or second-line setting (EPOC1706): an open-label, single-arm, phase 2 trial. Lancet Oncol.21(8), 1057–1065 (2020).
   PubMed Web of Science ®Google Scholar
• KoheiS , Ben-AharonI , RojasCet al.First-line lenvatinib (Len) + pembrolizumab (Pembro) + chemotherapy (Chemo) vs chemo in advanced/metastatic gastroesophageal adenocarcinoma: LEAP-015 safety run-in. Ann. Oncol.33, S1108 (2021).
   Google Scholar
• VictorAG , AnneVP , NaQet al.Trastuzumab Increases HER2 Uptake and Cross-Presentation by Dendritic Cells. Cancer Res.77(19), 5374–5383 (2017).
   PubMed Web of Science ®Google Scholar
• YelenaYJ , StevenBM , WalidKCet al.First-line pembrolizumab and trastuzumab in HER2-positive oesophageal, gastric, or gastro-oesophageal junction cancer: an open-label, single-arm, phase 2 trial. Lancet Oncol.21(6), 821–831 (2020).
   PubMed Web of Science ®Google Scholar
• YelenaYJ , AkihitoK , PatricioYet al.The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature600(7890), 727–730 (2021).
   PubMed Web of Science ®Google Scholar
• DaisukeT , HirokazuS , KeikoMet al.Safety and early efficacy results of a phase Ib study of nivolumab plus trastuzumab with S-1/capecitabine plus oxaliplatin for HER2-positive advanced gastric cancer (Ni-HIGH study). J. Clin. Oncol.40, 276–276 (2022).
   Web of Science ®Google Scholar
• ShanuM , CristinaS , ToshinariYet al.Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N. Engl. J. Med.382(7), 610–621 (2020).
   PubMed Web of Science ®Google Scholar
• EricVC , MarcoDB , ElizabethSet al.LBA55 Primary analysis of a phase II single-arm trial of trastuzumab deruxtecan (T-DXd) in western pa-tients (Pts) with HER2-positive (HER2+) unresectable or metastatic gastric or gastroesopha-geal junction (GEJ) cancer who progressed on or after a trastuzumab-containing regimen. Ann. Oncol.32, S1332 (2021).
   PubMed Web of Science ®Google Scholar
• DanielVTC , Yoon-KooK , HaeseongPet al.Margetuximab plus pembrolizumab in patients with previously treated, HER2-positive gastro-oesophageal adenocarcinoma (CP-MGAH22-05): a single-arm, phase 1b-2 trial. Lancet Oncol.21(8), 1066–1076 (2020).
   PubMed Web of Science ®Google Scholar
• DanielVC , MinoriR , HyunCCet al.MAHOGANY: margetuximab combination in HER2+ unresectable/metastatic gastric/gastroesophageal junction adenocarcinoma. Future Oncol.17(10), 1155–1164 (2021).
   PubMed Web of Science ®Google Scholar
• KuG , ElimovaE , DenlingerCet al.Phase (Ph) II study of zanidatamab + chemotherapy (chemo) in first-line (1L) HER2 expressing gastroesophageal adenocarcinoma (GEA). Ann. Oncol.32(Suppl. 5), S1044–S1045 (2021).
   Google Scholar
• TracyP , KarynB , DeborahAet al.In Vitro and in vivo activity of ARRY-380: a potent, small molecule inhibitor of ErbB2. Cancer Res.69(Suppl. 9), 1795 (2009).
   Google Scholar
• UgurS , MartinS , HeikeRet al.A phase I dose-escalation study of IMAB362 (Zolbetuximab) in patients with advanced gastric and gastro-oesophageal junction cancer. Eur. J. Cancer100, 7–26 (2018).
   Web of Science ®Google Scholar
• SahinU , TüreciÖ , ManikhasGet al.FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma. Ann. Oncol.32(5), 609–619 (2021).
   PubMed Web of Science ®Google Scholar
• KoheiS , FlorianL , Yung-JueBet al.Zolbetuximab + mFOLFOX6 as first-line (1L) treatment for patients (pts) with claudin-18.2+ (CLDN18.2+)/HER2- locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: primary results from phase 3 SPOTLIGHT study. J. Clin. Oncol.41(Suppl. 4), abstr LBA292 (2023).
   Google Scholar
• LawrencePA , ArielEM , CharlesGDet al.LAG3 (CD223) as a cancer immunotherapy target. Immunol. Rev.276(1), 80–96 (2017).
   PubMed Web of Science ®Google Scholar
• XinY , KristinH , LinoCGet al.The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat. Immunol.10(1), 48–57 (2009).
   PubMed Web of Science ®Google Scholar
• KoheiS , TaliaG , MilehamKet al.Phase 1 trial of vibostolimab plus pembrolizumab for PD-1/PD-L1 inhibitor-naive advanced gastric cancer: The KEYVIBE-001 trial. Ann. Oncol.33(Suppl. 4), S240 (2022).
   Google Scholar
• PatrickAB , PeterK , RalfB. BiTE: teaching antibodies to engage T-cells for cancer therapy. Curr. Opin. Mol. Ther.11(1), 22–30 (2009).
   PubMedGoogle Scholar
• DaisukeK , RyutaroA , HirokiKet al.Mechanism of action of a T cell-dependent bispecific antibody as a breakthrough immunotherapy against refractory colorectal cancer with an oncogenic mutation. Cancer Immunol. Immunother.70(1), 177–188 (2021).
   PubMed Web of Science ®Google Scholar
• ShannonLM , TheodoreWL , JochenBet al.Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N. Engl. J. Med.378(5), 439–448 (2018).
   PubMed Web of Science ®Google Scholar
• SattvaSN , FrederickLL , WilliamYG. CAR T-Cell Therapy in Large B-Cell Lymphoma. N. Engl. J. Med.378, 1065 (2018).
   Web of Science ®Google Scholar
• MiheH , JustinDC , YvonneYC. Engineering CAR-T Cells for Next-Generation Cancer Therapy. Cancer Cell38(4), 473–488 (2020).
   PubMed Web of Science ®Google Scholar
• ChangsongQ , JifangG , JianLet al.Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results. Nat. Med.28(6), 1189–1198 (2022).
   PubMed Web of Science ®Google Scholar