Acta Scientific Gastrointestinal Disorders (ISSN: 2582-1091)

Mini ReviewVolume 4 Issue 10

Pembrolizumab in the Treatment of Metastatic Gastric Cancer

Rakhimov R Radmir1*, AA Izmailov1, ON Lipatov1,2, AV Sultanbaev1, KV Menshikov1,2, AF Nasretdinov1 and VA Surovyatkin1

1State Autonomous Institution of Healthcare Republican Clinical Oncological Dispensary of the Ministry of Health of the Republic of Bashkortostan, Ufa, Russia
2Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Health of the Russian Federation, Russia

*Corresponding Author: Rakhimov R Radmir, State Autonomous Institution of Healthcare Republican Clinical Oncological Dispensary of the Ministry of Health of the Republic of Bashkortostan, Ufa, Russia.

Received: September 02, 2021; Published: September 20, 2021

Citation: Rakhimov R Radmir., et al. “Pembrolizumab in the Treatment of Metastatic Gastric Cancer". Acta Scientific Gastrointestinal Disorders 4.10 (2021): 20-31.


  The incidence of stomach cancer has been declining over the past decade, but unfortunately it is still the fifth most common disease with the third death rate among cancers. Diagnosis of stomach cancer usually occurs at the stage of neglect and incurability (stages III - IV), in the early stages (I - II stages) clear symptoms do not appear. 25% of patients have advanced gastric cancer, the other 25 - 50% progress to metastatic gastric cancer. The prognosis is especially poor for patients who have not responded to 1 line of chemotherapy. In the United States in 2012, 54.5% of patients received second and third lines. Five-year survival rate is 30% among all stages. In recent years, new drugs have emerged in the treatment of stomach cancer that needs to be studied. Pembrolizumab demonstrated efficacy in PD-L1-positive advanced gastric/gastroesophageal junction cancer in the first-, second-, and third-line setting in KEYNOTE-062, KEYNOTE-061, and KEYNOTE-059, respectively.

  In KEYNOTE-062, median follow-up was 11 months, median OS (pembrolizumab vs. chemotherapy) was 17 months versus 11 months (HR, 0.69; 95% CI, 0.49-0.97), median PFS was 3 months versus 6 months (HR, 1.09, 95% CI; 0.79-1.49), ORR was 25% versus 38%, and median (range) DOR was 19 months (1+ to 34+) versus 7 months (2+ to 30+).

Keywords: Pembrolizumab; Gastric Cancer; Immune Therapy; Checkpoint Inhibitor; Systemic Therapy


  1. M Ayers., et al. “IFN-gamma-related mRNA profile predicts clinical response to PD-1 blockade”. Journal of Clinical Investigation 127 (2017): 2930-2940.
  2. C Boger., et al. “PD-L1 is an independent prognostic predictor in gastric cancer of Western patients”. Oncotarget 7 (2016): 24269-24283.
  3. H Chang., et al. “Programmed death-ligand 1 expression in gastric adenocarcinoma is a poor prognostic factor in a high CD8+ tumor infiltrating lymphocytes group”. Oncotarget 7 (2016): 80426-80434.
  4. R Cristescu., et al. “Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes”. Nature Medicine 21 (2015): 449-456.
  5. L Gu., et al. “PD-L1 and gastric cancer prognosis: a systematic review and meta-analysis”. PLoS One 12 (2017): e0182692.
  6. CG Jiang., et al. “Clinicopathologic characteristics and prognosis of signet ring cell carcinoma of the stomach: results from a Chinese mono-institutional study”. Journal of Surgical Oncology 103 (2011): 700-703.
  7. S Jin., et al. “The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in advanced gastric signet-ring cell carcinoma, representing a potential biomarker for immunotherapy”. Oncotarget 8 (2017): 38850-38862.
  8. A Kawazoe., et al. “Clinicopathological features of programmed death ligand 1 expression with tumor-infiltrating lymphocyte, mismatch repair, and Epstein-Barr virus status in a large cohort of gastric cancer patients”. Gastric Cancer 3 (2017): 407-415.
  9. K Yuza., et al. “Hypermutation and microsatellite instability in gastrointestinal cancers”. Oncotarget 67 (2017): 112103-112115.
  10. ST Kim., et al. “Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer”. Nature Medicine 24 (2018): 1449-1458.
  11. J Lee and K Kim. “Biomarkers for gastric cancer: molecular classification revisited”. Precision and Future Medicine 1 (2017): 59-68.
  12. S Lemery., et al. “First FDA approval agnostic of cancer site - when a biomarker defines the indication”. The New England Journal of Medicine 377 (2017): 1409-1412.
  13. YX Liu., et al. “Prognostic significance of PD-L1 expression in patients with gastric cancer in East Asia: a meta-analysis”. Oncology and Therapy 9 (2016): 2649-2654.
  14. K Yuza., et al. “Hypermutation and microsatellite instability in gastrointestinal cancers”. Oncotarget 8 (2017): 112103-112115.
  15. X Liua., et al. “High PD-L1 expression in gastric cancer (GC) patients and correlation with molecular features”. Pathology - Research and Practice 216 (2020): 1-7.
  16. Salem ME., et al. “Landscape of tumor mutation load, mismatch repair deficiency, and PD-L1 expression in a large patient cohort of gastrointestinal cancers”. Molecular Cancer Research 16 (2018): 805-812.
  17. Bonneville R., et al. “Landscape of microsatellite instability across 39 cancer types”. JCO Precision Oncology - ASCO Journals (2017).
  18. Nakamura Y., et al. “Large-scale analyses of tumor mutation burdens (TMBs) across various advanced gastrointestinal (GI) malignancies in the nationwide cancer genome screening project SCRUM-Japan GI-SCREEN”. Journal of Clinical Oncology 36 (2018): 12094.
  19. Liu Y., et al. “Comparative molecular analysis of gastrointestinal adenocarcinomas”. Cancer Cell 33 (2018): 721-735.
  20. Network CGAR. “Comprehensive molecular characterization of gastric adenocarcinoma”. Nature 513 (2014): 202-209.
  21. Y Eso., et al. “Microsatellite instability and immune checkpoint inhibitors: toward precision medicine against gastrointestinal and hepatobiliary cancers”. The Journal of Gastroenterology 55 (2020): 15-26.
  22. Chalmers ZR., et al. “Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden”. Genome Medicine 9 (2017): 34.
  23. Kang YK., et al. “Nivolumab in patients with advanced gastric or gastrooesophageal 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 390 (2017): 2461-2471.
  24. Boku N., et al. “A phase 3 study of nivolumab (Nivo) in previously treated advanced gastric or gastroesophageal junction (G/GEJ) cancer: Updated results and subset analysis by PD-L1expression (ATTRACTION-02)”. Annals of Oncology5 (2017): 617OA.
  25. BA Weinberg., et al. “Immuno-Oncology Biomarkers for Gastric and Gastroesophageal Junction Adenocarcinoma: Why PD-L1 Testing May Not Be Enough”. The Oncologist 23 (2018): 1-7.
  26. Muro K., et al. “Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial”. Lancet Oncology6 (2016): 717-726.
  27. Kim ST., et al. “Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer”. Nature Medicine9. (2018): 1449-1458.
  28. Le DT., et al. “PD-1 blockade in tumors with mismatch-repair deficiency”. The New England Journal of Medicine26 (2015): 2509-2520.
  29. Sundar R., et al. “Transcriptional analysis of immune genes in Epstein-Barr virus-associated gastric cancer and association with clinical outcomes”. Gastric Cancer6 (2018): 1064-1070.
  30. R Sundar., et al. “Epigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer”. Annals of Oncology 30 (2019): 424-430.
  31. SV Menghani., et al. “Gastric cardia adenocarcinoma with metastasis to the scalp: a case report”. Cureus1 (2020).
  32. G Brar and MA Shah. “The role of pembrolizumab in the treatment of PD-L1 expressing gastric and gastroesophageal junction adenocarcinoma”. Therapeutic Advances in Gastroenterology 12 (2019): 1-12.
  33. SS Joshi., et al. “Pembrolizumab for treatment of advanced gastric and gastroesophageal junction adenocarcinoma”. Future Oncology 5 (2018): 417-430.
  34. I Chau., et al. “Ramucirumab in Combination with Pembrolizumab in Treatment-Naïve Advanced Gastric or GEJ Adenocarcinoma: Safety and Antitumor Activity from the Phase 1a/b JVDF Trial”. Cancers 12 (2020): 1-16.
  35. Ohtsu A., et al. “Pembrolizumab (MK-3475) versus paclitaxel as second-line therapy for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: Phase III KEYNOTE-061 study”. Journal of Clinical Oncology 4 (2016): TPS183-TPS183.
  36. Doi T., et al. “KEYNOTE-181: Phase 3, open-label study of second-line pembrolizumab vs single-agent chemotherapy in patients with advanced/metastatic esophageal adenocarcinoma”. Journal of Clinical Oncology 15 (2016): TPS4140-TPS4140.
  37. Bang YJ., et al. “First-in-human Phase 1 study of margetuximab (MGAH22), an Fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors”. Annals of Oncology4 (2017): 855-861.
  38. Catenacci DVT., et al. “A Phase 1b/2, open label, dose-escalation study of margetuximab (M) in combination with pembrolizumab (P) in patients with relapsed/refractory advanced HER2+ gastroesophageal (GEJ) junction or gastric (G) cancer”. Journal of Clinical Oncology4 (2017): TPS219-TPS219.
  39. Shah MA., et al. “Pembrolizumab (MK-3475) for previously treated metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: Phase II KEYNOTE-180 study”. Journal of Clinical Oncology4 (2016): TPS189-TPS189.
  40. Deng L., et al. “Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice”. Journal of Clinical Investigation2 (2014): 687-695.
  41. Chao J., et al. “Combining pembrolizumab and palliative radiotherapy in gastroesophageal cancer to enhance anti-tumor T-cell response and augment the abscopal effect”. Journal of Clinical Oncology4 (2017): TPS220-TPS220.
  42. Phase 1b open-label study of PEGPH20 with pembrolizumab.
  43. Safety and efficacy of CRS-207 with pembrolizumab in gastric, gastroesophageal junction or esophageal cancers.
  44. Rimm DL., et al. “A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer”. JAMA Oncology8 (2017): 1051-1058.
  45. Tran PN., et al. “PD-1 and PD-L1 as emerging therapeutic targets in gastric cancer: current evidence”. Gastrointestinal Cancer 7 (2017): 1-11.
  46. Farris AB 3rd., et al. “Clinicopathologic and molecular profiles of microsatellite unstable Barrett Esophagus-associated adenocarcinoma”. The American Journal of Surgical Pathology5 (2011): 647-655.
  47. Zhu L., et al. “Microsatellite instability and survival in gastric cancer: a systematic review and meta-analysis”. Molecular and Clinical Oncology3 (2015): 699-705.
  48. Smyth EC., et al. “Mismatch repair deficiency, microsatellite instability, and survival: an exploratory analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) Trial”. JAMA Oncology9 (2017): 1197-1203.
  49. Gryfe R., et al. “Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer”. The New England Journal of Medicine2 (2000): 69-77.
  50. Dudley JC., et al. “Microsatellite instability as a biomarker for PD-1 blockade”. Clinical Cancer Research4 (2016): 813-820.

Copyright: © Rakhimov R Radmir., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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