Immunotherapy in Gastric Cancer

Anica Högner, Markus Moehler, Anica Högner, Markus Moehler

Abstract

Immune checkpoint inhibition is a new standard of targeted therapy in the treatment of advanced or metastatic gastric cancer (GC) and is represented in various combinations with and without chemotherapy in every therapy line within clinical trials. In advanced adenocarcinoma of GC, gastroesophageal junction cancer (GEJC) and esophageal cancer (EC), the combination of nivolumab and chemotherapy in first-line therapy improves overall survival (OS) in PD-L1 (programmed cell death protein 1)-positive patients with approval in Europe (PD-L1 CPS (combined positivity score) ≥ 5), USA and Taiwan (CHECKMATE-649) and pembrolizumab plus chemotherapy for GEJC and EC in Europe (CPS ≥ 10) and the USA (KEYNOTE-590). Furthermore, pembrolizumab plus trastuzumab and chemotherapy show clear benefits in OS and are approved as first-line treatment of Her2 (human epidermal growth factor receptor-2)-positive tumors in the USA (KEYNOTE-811). Nivolumab demonstrates superior OS regardless of PD-L1 expression in third-line therapy with approval in Japan (ATTRACTION-02) and pembrolizumab prolonged the duration of response in PD-L1 positive patients with approval in the USA in PD-L1 CPS ≥ 1 patients (KEYNOTE-059). This review reflects the rationale and current results of phase II and III clinical trials investigating various immune checkpoint inhibitors targeting PD-L1/1 and CTLA (anticytotoxic T-lymphocyte-associated antigen)-4 in combination with and without chemotherapy and Her2-targeted therapy in GC.

Keywords: CTLA-4; Her2-positive; PD-1; PD-L1; checkpoint inhibition; esophagogastric cancer; gastric cancer; immunotherapy; trastuzumab.

Conflict of interest statement

A.H. was a member of the advisory board of BMS. M.M. advisory roles for BMS, MSD, Merck, Amgen, BeiGene, Novartis, Lilly, Macrogenics, Sanofi, Servier and Roche.

Figures

Figure 1
Figure 1
New therapeutic strategies in advanced esophagogastric adenocarcinoma (Europe). Chemo = chemotherapy, PD-L1 CPS = programmed cell death protein 1 (combined positivity score), BSC = best supportive care.

References

    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660.
    1. Ferlay J., Colombet M., Soerjomataram I., Dyba T., Randi G., Bettio M., Gavin A., Visser O., Bray F. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur. J. Cancer. 2018;103:356–387. doi: 10.1016/j.ejca.2018.07.005.
    1. Stomach Cancer—Statistics. [(accessed on 27 December 2021)]. Available online: .
    1. Palle J., Rochand A., Pernot S., Gallois C., Taïeb J., Zaanan A. Human epidermal growth factor receptor 2 (HER2) in advanced gastric cancer: Current knowledge and future perspectives. Drugs. 2020;80:401–415. doi: 10.1007/s40265-020-01272-5.
    1. Bang Y.-J., Van Cutsem E., Feyereislova A., Chung H.C., Shen L., Sawaki A., Lordick F., Ohtsu A., Omuro Y., Satoh T., et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–697. doi: 10.1016/S0140-6736(10)61121-X.
    1. Janjigian Y.Y., Kawazoe A., Yanez P.E., Luo S., Lonardi S., Kolesnik O., Barajas O., Bai Y., Shen L., Tang Y., et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (G/GEJ) Cancer: Initial findings of the global phase 3 KEYNOTE-811 study. J. Clin. Oncol. 2021;39:4013. doi: 10.1200/JCO.2021.39.15_suppl.4013.
    1. Ricci A.D., Rizzo A., Rojas Llimpe F.L., Di Fabio F., De Biase D., Rihawi K. Novel HER2-directed treatments in advanced gastric carcinoma: AnotHER paradigm shift? Cancers. 2021;13:1664. doi: 10.3390/cancers13071664.
    1. Shitara K., Iwata H., Takahashi S., Tamura K., Park H., Modi S., Tsurutani J., Kadowaki S., Yamaguchi K., Iwasa S., et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive gastric cancer: A dose-expansion, phase 1 study. Lancet Oncol. 2019;20:827–836. doi: 10.1016/S1470-2045(19)30088-9.
    1. Janjigian Y.Y., Oh D.-Y., Rha S.Y., Lee K.W., Steeghs N., Chao Y., Di Bartolomeo M., Díez Garcia M., Haj Mohammad N., Stein A., et al. Dose-escalation and dose-expansion study of trastuzumab deruxtecan (T-DXd) monotherapy and combinations in patients (Pts) with advanced/metastatic HER2+ gastric cancer (GC)/gastroesophageal junction adenocarcinoma (GEJA): DESTINY-Gastric03. J. Clin. Oncol. 2022;40:295. doi: 10.1200/JCO.2022.40.4_suppl.295.
    1. Catenacci D.V.T., Kang Y.-K., Park H., Uronis H.E., Lee K.-W., Ng M.C.H., Enzinger P.C., Park S.H., Gold P.J., Lacy J., et 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. 2020;21:1066–1076. doi: 10.1016/S1470-2045(20)30326-0.
    1. Catenacci D.V.T., Rosales M.K., Chung H.C., Yoon H.H., Shen L., Moehler M.H., Kang Y.-K. Margetuximab (M) combined with anti-PD-1 (retifanlimab) or anti-PD-1/LAG-3 (tebotelimab) +/− chemotherapy (CTX) in first-line therapy of advanced/metastatic HER2+ gastroesophageal junction (GEJ) or gastric cancer (GC) J. Clin. Oncol. 2021;39:TPS264. doi: 10.1200/JCO.2021.39.3_suppl.TPS264.
    1. Rizzo A., Mollica V., Ricci A.D., Maggio I., Massucci M., Rojas Limpe F.L., Fabio F.D., Ardizzoni A. Third- and later-line treatment in advanced or metastatic gastric cancer: A systematic review and meta-analysis. Future Oncol. 2020;16:4409–4418. doi: 10.2217/fon-2019-0429.
    1. Al-Batran S.-E., Lorenzen S., Thuss-Patience P.C., Schenk M., Goekkurt E., Hofheinz R.D., Kretzschmar A., Heuer V., Bolling C., Haag G.M., et al. 1494P updated safety data of the DANTE trial: Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma—A randomized, open-label phase II trial of the German Gastric Group at the AIO and SAKK. Ann. Oncol. 2020;31:S927–S928. doi: 10.1016/j.annonc.2020.08.2000.
    1. Smyth E., Knödler M., Giraut A., Mauer M., Nilsson M., Van Grieken N., Wagner A.D., Moehler M., Lordick F. VESTIGE: Adjuvant immunotherapy in patients with resected esophageal, gastroesophageal junction and gastric cancer following preoperative chemotherapy with high risk for recurrence (N+ and/or R1): An open label randomized controlled phase-2-study. Front. Oncol. 2020;9:1320. doi: 10.3389/fonc.2019.01320.
    1. Bang Y.-J., Van Cutsem E., Fuchs C.S., Ohtsu A., Tabernero J., Ilson D.H., Hyung W.J., Strong V.E., Goetze T.O., Yoshikawa T., et al. KEYNOTE-585: Phase III study of perioperative chemotherapy with or without pembrolizumab for gastric cancer. Future Oncol. 2019;15:943–952. doi: 10.2217/fon-2018-0581.
    1. Janjigian Y.Y., Van Cutsem E., Muro K., Wainberg Z.A., Al-Batran S.-E., Hyung W.J., Molena D., Evans B., Ruscica D., Robbins S.H., et al. MATTERHORN: Efficacy and safety of neoadjuvant-adjuvant durvalumab and FLOT chemotherapy in resectable gastric and gastroesophageal junction cancer—A randomized, double-blind, placebo-controlled, phase 3 study. J. Clin. Oncol. 2021;39:TPS4151. doi: 10.1200/JCO.2021.39.15_suppl.TPS4151.
    1. Janjigian Y.Y., Shitara K., Moehler M., Garrido M., Salman P., Shen L., Wyrwicz L., Yamaguchi K., Skoczylas T., Campos Bragagnoli A., et 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. Lancet. 2021;398:27–40. doi: 10.1016/S0140-6736(21)00797-2.
    1. Boku N., Ryu M.-H., Kato K., Chung H.C., Minashi K., Lee K.-W., Cho H., Kang W.K., Komatsu Y., Tsuda M., et al. Safety and efficacy of nivolumab in combination with S-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: Interim results of a randomized, phase II trial (ATTRACTION-4) Ann. Oncol. 2019;30:250–258. doi: 10.1093/annonc/mdy540.
    1. Sun J.-M., Shen L., Shah M.A., Enzinger P., Adenis A., Doi T., Kojima T., Metges J.-P., Li Z., Kim S.-B., et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): A randomised, placebo-controlled, phase 3 study. Lancet. 2021;398:759–771. doi: 10.1016/S0140-6736(21)01234-4.
    1. Shitara K., Van Cutsem E., Bang Y.-J., Fuchs C., Wyrwicz L., Lee K.-W., Kudaba I., Garrido M., Chung H.C., Lee J., et 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. 2020;6:1571–1580. doi: 10.1001/jamaoncol.2020.3370.
    1. Tabernero J., Bang Y.-J., Van Cutsem E., Fuchs C.S., Janjigian Y.Y., Bhagia P., Li K., Adelberg D., Qin S.K. KEYNOTE-859: A phase III study of pembrolizumab plus chemotherapy in gastric/gastroesophageal junction adenocarcinoma. Future Oncol. 2021;17:2847–2855. doi: 10.2217/fon-2021-0176.
    1. Moehler M.H., Dvorkin M., Ozguroglu M., Ryu M., Muntean A.S., Lonardi S., Nechaeva M., Campos Bragagnoli A.S., Coskun H.S., Cubillo Gracián A., et al. Results of the JAVELIN gastric 100 phase 3 trial: Avelumab maintenance following first-line (1L) chemotherapy (CTx) vs continuation of CTx for HER2− advanced gastric or gastroesophageal junction cancer (GC/GEJC) J. Clin. Oncol. 2020;38:278. doi: 10.1200/JCO.2020.38.4_suppl.278.
    1. Xu J., Jiang H., Pan Y., Gu K., Cang S., Han L., Shu Y., Li J., Zhao J., Pan H., et al. LBA53 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. 2021;32:S1331. doi: 10.1016/j.annonc.2021.08.2133.
    1. Xu R., Arkenau H.-T., Bang Y.-J., Denlinger C.S., Kato K., Tabernero J., Wang J., Li J., Castro H., Moehler M.H. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line therapy in patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. J. Clin. Oncol. 2020;38:TPS458. doi: 10.1200/JCO.2020.38.4_suppl.TPS458.
    1. Shitara K., Özgüroğlu M., Bang Y.-J., Di Bartolomeo M., Mandalà M., Ryu M.-H., Fornaro L., Olesiński T., Caglevic C., Chung H.C., et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): A randomised, open-label, controlled, phase 3 trial. Lancet. 2018;392:123–133. doi: 10.1016/S0140-6736(18)31257-1.
    1. Högner A., Breithaupt K., Stein A., Hinke A., Lorenz M., Al-Batran S.-E., Thuss-Patience P.C. RAP: A phase II trial with ramucirumab, avelumab, and paclitaxel as second line treatment in gastro-esophageal adenocarcinoma of the arbeitsgemeinschaft internistische onkologie (AIO) J. Clin. Oncol. 2019;37:TPS4148. doi: 10.1200/JCO.2019.37.15_suppl.TPS4148.
    1. Kang Y.-K., Boku N., Satoh T., Ryu M.-H., Chao Y., Kato K., Chung H.C., Chen J.-S., Muro K., Kang W.K., et 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. Lancet. 2017;390:2461–2471. doi: 10.1016/S0140-6736(17)31827-5.
    1. Fuchs C.S., Doi T., Jang R.W.-J., Muro K., Satoh T., Machado M., Sun W., Jalal S.I., Shah M.A., Metges J.-P., et al. KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer. J. Clin. Oncol. 2017;35:4003. doi: 10.1200/JCO.2017.35.15_suppl.4003.
    1. Bang Y.-J., Ruiz E.Y., Van Cutsem E., Lee K.-W., Wyrwicz L., Schenker M., Alsina M., Ryu M.-H., Chung H.-C., Evesque L., et 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. 2018;29:2052–2060. doi: 10.1093/annonc/mdy264.
    1. Stein A., Paschold L., Tintelnot J., Goekkurt E., Thuss-Patience P.C., Lorenzen S., Ettrich T.J., Knorrenschild J.R., Jacobasch L., Kretzschmar A., et al. LBA54 ipilimumab or FOLFOX in combination with nivolumab and trastuzumab in previously untreated HER2 positive locally advanced or metastastic esophagogastric adenocarcinoma (EGA): Results of the randomized phase II INTEGA trial (AIO STO 0217) Ann. Oncol. 2021;32:S1331. doi: 10.1016/j.annonc.2021.08.2134.
    1. Janjigian Y.Y., Viglianti N., Liu F., Mendoza-Naranjo A., Croydon L. A phase Ib/II, multicenter, open-label, dose-escalation, and dose-expansion study evaluating trastuzumab deruxtecan (T-DXd, DS-8201) monotherapy and combinations in patients with HER2-overexpressing gastric cancer (DESTINY-Gastric03) J. Clin. Oncol. 2021;39:TPS261. doi: 10.1200/JCO.2021.39.3_suppl.TPS261.
    1. Al-Batran S.-E., Pauligk C., Hofheinz R., Lorenzen S., Wicki A., Siebenhuener A.R., Schenk M., Welslau M., Heuer V., Goekkurt E., et al. Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: DANTE, a randomized, open-label phase II trial of the German Gastric Group of the AIO and the SAKK. J. Clin. Oncol. 2019;37:TPS4142. doi: 10.1200/JCO.2019.37.15_suppl.TPS4142.
    1. Al-Batran S.-E., Homann N., Pauligk C., Goetze T.O., Meiler J., Kasper S., Kopp H.-G., Mayer F., Haag G.M., Luley K., et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or Capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2/3 trial. Lancet. 2019;393:1948–1957. doi: 10.1016/S0140-6736(18)32557-1.
    1. Chen L.-T., Kang Y.-K., Tanimoto M., Boku N. ATTRACTION-04 (ONO-4538-37): A randomized, multicenter, phase 2/3 study of nivolumab (Nivo) plus chemotherapy in patients (Pts) with previously untreated advanced or recurrent gastric (G) or gastroesophageal junction (GEJ) cancer. Ann. Oncol. 2017;28:v266. doi: 10.1093/annonc/mdx369.159.
    1. Wainberg Z.A., Shitara K., Van Cutsem E., Wyrwicz L., Lee K.W., Kudaba I., Garrido M., Chung H.C.C., Lee J., Castro-Salguero H.R., et al. Pembrolizumab with or without chemotherapy versus chemotherapy alone for patients with PD-L1–positive advanced gastric or gastroesophageal junction adenocarcinoma: Update from the phase 3 KEYNOTE-062 trial. J. Clin. Oncol. 2022;40:243. doi: 10.1200/JCO.2022.40.4_suppl.243.
    1. Shitara K., Özgüroğlu M., Bang Y.-J., Di Bartolomeo M., Mandalà M., Ryu M., Vivaldi C., Olesinski T., Chung H.C., Muro K., et al. The association of tissue tumor mutational burden (TTMB) using the foundation medicine genomic platform with efficacy of pembrolizumab versus paclitaxel in patients (Pts) with gastric cancer (GC) from KEYNOTE-061. J. Clin. Oncol. 2020;38:4537. doi: 10.1200/JCO.2020.38.15_suppl.4537.
    1. Smyth E.C., Verheij M., Allum W., Cunningham D., Cervantes A., Arnold D., ESMO Guidelines Committee Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2016;27:v38–v49. doi: 10.1093/annonc/mdw350.
    1. Hofheinz R.-D., Hegewisch-Becker S., Kunzmann V., Thuss-Patience P., Fuchs M., Homann N., Graeven U., Schulte N., Merx K., Pohl M., et al. Trastuzumab in combination with 5-fluorouracil, leucovorin, oxaliplatin and docetaxel as perioperative treatment for patients with human epidermal growth factor receptor 2-positive locally advanced esophagogastric adenocarcinoma: A phase II trial of the Arbeitsgemeinschaft Internistische Onkologie Gastric Cancer Study Group. Int. J. Cancer. 2021;149:1322–1331. doi: 10.1002/ijc.33696.
    1. Janjigian Y.Y., Maron S.B., Chatila W.K., Millang B., Chavan S.S., Alterman C., Chou J.F., Segal M.F., Simmons M.Z., Momtaz P., et 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. 2020;21:821–831. doi: 10.1016/S1470-2045(20)30169-8.
    1. Tintelnot J., Goekkurt E., Binder M., Thuss-Patience P., Lorenzen S., Knorrenschild J.R., Kretzschmar A., Ettrich T., Lindig U., Jacobasch L., et al. Ipilimumab or FOLFOX with nivolumab and trastuzumab in previously untreated HER2-positive locally advanced or metastatic EsophagoGastric adenocarcinoma—The randomized phase 2 INTEGA trial (AIO STO 0217) BMC Cancer. 2020;20:503. doi: 10.1186/s12885-020-06958-3.
    1. Catenacci D.V., Park H., Shim B.Y., Kim S.T., Oh D.-Y., Spira A., Ulahannan S., Avery E.J., Boland P.M., Chao J., et al. 1379P margetuximab (M) with retifanlimab (R) in HER2+, PD-L1+ 1st-line unresectable/metastatic gastroesophageal adenocarcinoma (GEA): MAHOGANY cohort, A. Ann. Oncol. 2021;32:S1043–S1044. doi: 10.1016/j.annonc.2021.08.1488.
    1. Saeki H., Oki E., Kashiwada T., Arigami T., Makiyama A., Iwatsuki M., Narita Y., Satake H., Matsuda Y., Sonoda H., et al. Re-evaluation of HER2 status in patients with HER2-positive advanced or recurrent gastric cancer refractory to trastuzumab (KSCC1604) Eur. J. Cancer. 2018;105:41–49. doi: 10.1016/j.ejca.2018.09.024.
    1. Catenacci D.V.T., Park H., Uronis H.E., Kang Y.-K., Lacy J., Enzinger P.C., Park S.H., Lee K.W., Ng M.C.H., Gold P.J., et al. Margetuximab (M) plus pembrolizumab (P) in ERBB2-amplified PD-L1+ gastroesophageal adenocarcinoma (GEA) post trastuzumab (T) J. Clin. Oncol. 2018;36:4030. doi: 10.1200/JCO.2018.36.15_suppl.4030.
    1. Panda A., Mehnert J.M., Hirshfield K.M., Riedlinger G., Damare S., Saunders T., Kane M., Sokol L., Stein M.N., Poplin E., et al. Immune activation and benefit from avelumab in EBV-positive gastric cancer. J. Natl. Cancer Inst. 2017;110:316–320. doi: 10.1093/jnci/djx213.
    1. Wainberg Z.A., Fuchs C.S., Tabernero J., Shitara K., Muro K., Van Cutsem E., Bang Y.-J., Chung H.C., Yamaguchi K., Varga E., et al. Efficacy of pembrolizumab monotherapy for advanced gastric/gastroesophageal junction cancer with programmed death ligand 1 combined positive score ≥10. Clin. Cancer Res. 2021;27:1923–1931. doi: 10.1158/1078-0432.CCR-20-2980.
    1. Zhao J.J., Yap D.W.T., Chan Y.H., Tan B.K.J., Teo C.B., Syn N.L., Smyth E.C., Soon Y.Y., Sundar R. Low programmed death-ligand 1–expressing subgroup outcomes of first-line immune checkpoint inhibitors in gastric or esophageal adenocarcinoma. J. Clin. Oncol. 2022;40:392–402. doi: 10.1200/JCO.21.01862.
    1. Yoon H.H., Jin Z., Kour O., Shitara K., Gibson M.K., Prokop L., Kang Y.-K., Shi Q., Ajani J.A. Association of magnitude and consistency of PD-L1 expression and other variables associated with benefit from Immune Checkpoint Inhibition (ICI): Systematic review and meta-analysis of 14 phase 3 trials in advanced gastroesophageal cancer (GEC) J. Clin. Oncol. 2022;40:344. doi: 10.1200/JCO.2022.40.4_suppl.344.
    1. Cancer Genome Atlas Research Network Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513:202–209. doi: 10.1038/nature13480.
    1. Di Bartolomeo M., Morano F., Raimondi A., Miceli R., Corallo S., Tamborini E., Perrone F., Antista M., Niger M., Pellegrinelli A., et al. Prognostic and predictive value of microsatellite instability, inflammatory reaction and PD-L1 in gastric cancer patients treated with either adjuvant 5-FU/LV or sequential FOLFIRI followed by cisplatin and docetaxel: A translational analysis from the ITACA-S trial. Oncologist. 2020;25:e460–e468. doi: 10.1634/theoncologist.2019-0471.
    1. Pietrantonio F., Randon G., Bartolomeo M.D., Luciani A., Chao J., Smyth E.C., Petrelli F. Predictive role of microsatellite instability for PD-1 blockade in patients with advanced gastric cancer: A meta-analysis of randomized clinical trials. ESMO Open. 2021;6:100036. doi: 10.1016/j.esmoop.2020.100036.
    1. Pietrantonio F., Raimondi A., Choi Y.Y., Kang W., Langley R.E., Kim Y.W., Kim K.-M., Nankivell M.G., Perrone F., Kook M.-C., et al. MSI-GC-01: Individual patient data (IPD) meta-analysis of microsatellite instability (MSI) and gastric cancer (GC) from four randomized clinical trials (RCTs) J. Clin. Oncol. 2019;37:66. doi: 10.1200/JCO.2019.37.4_suppl.66.
    1. Al-Batran S.-E., Lorenzen S., Homann N., Thuss-Patience P.C., Schenk M., Lindig U., Kretzschmar A., Heuer V., Goekkurt E., Haag G.M., et al. 1429P pathological regression in patients with microsatellite instability (MSI) receiving perioperative atezolizumab in combination with FLOT vs. FLOT alone for resectable esophagogastric adenocarcinoma: Results from the DANTE trial of the German Gastric Group at the AIO and SAKK. Ann. Oncol. 2021;32:S1069. doi: 10.1016/j.annonc.2021.08.1538.
    1. Andre T., Tougeron D., Piessen G., De La Fouchardiere C., Louvet C., Adenis A., Jary M., Tournigand C., Aparicio T., Desrame J., et al. Neoadjuvant nivolumab plus ipilimumab and adjuvant nivolumab in patients (Pts) with localized microsatellite instability-high (MSI)/mismatch repair deficient (DMMR) oeso-gastric adenocarcinoma (OGA): The GERCOR NEONIPIGA phase II study. J. Clin. Oncol. 2022;40:244. doi: 10.1200/JCO.2022.40.4_suppl.244.
    1. Tang W., Morgan D.R., Meyers M.O., Dominguez R.L., Martinez E., Kakudo K., Kuan P.F., Banet N., Muallem H., Woodward K., et al. Epstein-barr virus infected gastric adenocarcinoma expresses latent and lytic viral transcripts and has a distinct human gene expression profile. Infect. Agents Cancer. 2012;7:21. doi: 10.1186/1750-9378-7-21.
    1. Liu X., Choi M.G., Kim K., Kim K.-M., Kim S.T., Park S.H., Cristescu R., Peter S., Lee J. High PD-L1 expression in gastric cancer (GC) patients and correlation with molecular features. Pathol. Res. Pract. 2020;216:152881. doi: 10.1016/j.prp.2020.152881.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe