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Journal of Cancer Research and Clinical Oncology
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Open Access 01-12-2024 | Case Report

Efficacy of sintilimab combined with neoadjuvant chemotherapy and trastuzumab in conversional treatment of locally advanced HER2-positive gastric cancer: case analysis and literature review

Authors: Sidikjan Ibrahim, Amina Maimaitiaili, Guangsheng Zhu, Shengwei Ye

Published in: Journal of Cancer Research and Clinical Oncology | Issue 12/2024

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Abstract

Background

Regional lymph nodes that are fixed and fused into clusters or those exhibiting metastases outside the regional lymph nodes are generally classified as stage IV (M1) or unresectable. Patients with such nodes almost always need pre-operative treatment so that they can undergo surgical resection. Combining immunotherapy with trastuzumab and chemotherapy significantly improved the prognosis of HER-2 positive gastric/gastroesophageal junction (G/GEJ) cancer. However, very few reports are available on the role of immunotherapy in converting patients with unresectable cancer to resectable cancer.

Methods

In this study, we report on four patients with GC who were preoperatively treated with a combination of sintilimab, trastuzumab, and chemotherapy at Hubei Cancer Hospital, China, from January 2022 to October 2023. Both preoperative and postoperative clinical and pathological characteristics of each patient were analyzed. The preoperative tumor stage was cT4N3M1.

Results

Postoperative pathological results showed that two patients achieved pathological complete remission (pCR), while the pathological stage in the other two patients decreased to ypT1N0M0 and ypT2N0M0. None of them had nerve or vascular invasion. None of the patients had recurrences or metastases until the last follow-up (October 2024) after primary surgery. The present case report suggests that a combination of immunotherapy comprising trastuzumab and chemotherapy can improve the efficiency of conversion therapy for patients with HER-2 positive locally advanced G/GEJ cancer. This study also demonstrates the safety of immune checkpoint inhibitors in a conversional treatment approach.

Conclusion

We showed that a pathological complete response (pCR) can be obtained even with unresectable advanced GC through treatment with sintilimab combined with neoadjuvant chemotherapy and trastuzumab.
Literature
Al-Batran SE et al (2019) 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 393:1948–1957CrossRefPubMed
Augustin JE, Soussan P, Bass AJ (2022) Targeting the complexity of ERBB2 biology in gastroesophageal carcinoma. Ann Oncol 33:1134–1148CrossRefPubMed
Bang YJ et al (2010) 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 376:687–697CrossRefPubMed
Catenacci DVT., et al., (2020) 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: 1066–1076.
Chao J et al (2021) 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 7:895–902CrossRefPubMedPubMedCentral
Clynes RA et al (2000) Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med 6:443–446CrossRefPubMed
Fuchs CS et al (2018) 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:e180013CrossRefPubMedPubMedCentral
Fuchs CS et al (2022) 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 Cancer 25:197–206CrossRefPubMed
Gong J et al (2016) Optimal regimen of trastuzumab in combination with oxaliplatin/ capecitabine in first-line treatment of HER2-positive advanced gastric cancer (CGOG1001): a multicenter, phase II trial. BMC Cancer 16:68CrossRefPubMedPubMedCentral
Jaime-Ramirez AC et al (2011) IL-12 enhances the antitumor actions of trastuzumab via NK cell IFN-γ production. J Immunol 186:3401–3409CrossRefPubMed
Janjigian YY et al (2020) 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 21:821–831CrossRefPubMedPubMedCentral
Janjigian YY et al (2021a) 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 398:27–40CrossRefPubMedPubMedCentral
Japanese Gastric Cancer Treatment Guidelines (2021) 6th edition. Gastric Cancer 26(1–25):2023
Kamada T et al (2019) PD-1(+) regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer. Proc Natl Acad Sci USA 116:9999–10008CrossRefPubMedPubMedCentral
Kang YK et al (2017) 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 390:2461–2471CrossRefPubMed
Kang YK et al (2022) 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 23:234–247CrossRefPubMed
Kurokawa Y et al (2014) Phase II study of trastuzumab in combination with S-1 plus cisplatin in HER2-positive gastric cancer (HERBIS-1). Br J Cancer 110:1163–1168CrossRefPubMedPubMedCentral
Lee CK et al (2022) A single arm phase Ib/II trial of first-line pembrolizumab, trastuzumab and chemotherapy for advanced HER2-positive gastric cancer. Nat Commun 13:6002CrossRefPubMedPubMedCentral
Liu T et al (2023) First-line nivolumab plus chemotherapy vs chemotherapy in patients with advanced gastric, gastroesophageal junction and esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis. Int J Cancer 152:749–760CrossRefPubMed
Lordick F et al., (2022) Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 33: 1005–1020,.
Marabelle A et al (2020) 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 38:1–10CrossRefPubMed
Miura Y et al (2018) Five-weekly S-1 plus cisplatin therapy combined with trastuzumab therapy in HER2-positive gastric cancer: a phase II trial and biomarker study (WJOG7212G). Gast Cancer 21:84–95CrossRef
Müller P, et al., (2015) Trastuzumab emtansine (T-DM1) renders HER2+ breast cancer highly susceptible to CTLA-4/PD-1 blockade. Sci Transl Med 7: 315ra188.
Muro K et al (2016) Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol 17:717–726CrossRefPubMed
Oh DY, Bang YJ (2020) HER2-targeted therapies - a role beyond breast cancer. Nat Rev Clin Oncol 17:33–48CrossRefPubMed
Rodriquenz MG., et al., (2020) MSI and EBV positive gastric cancer's subgroups and their link with novel immunotherapy. J Clin Med 9, 1427.
Shitara K et al (2020) 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 6:1571–1580CrossRefPubMed
Stagg J et al (2011) Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy. Proc Natl Acad Sci USA 108:7142–7147CrossRefPubMedPubMedCentral
Sung H et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71:209–249CrossRefPubMed
Taylor C et al (2007) Augmented HER-2 specific immunity during treatment with trastuzumab and chemotherapy. Clin Cancer Res 13:5133–5143CrossRefPubMed
Wang FH et al (2021) The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2021. Cancer Commun 41:747–795CrossRef
Yamashita K et al (2021) Trastuzumab upregulates programmed death ligand-1 expression through interaction with NK cells in gastric cancer. Br J Cancer 124:595–603CrossRefPubMed
Yuki S et al (2020) Multicenter phase II study of SOX plus trastuzumab for patients with HER2(+) metastatic or recurrent gastric cancer: KSCC/HGCSG/CCOG/PerSeUS 1501B. Cancer Chemother Pharmacol 85:217–223CrossRefPubMed
Zhu Y et al (2021) HER2-targeted therapies in gastric cancer. Biochim Biophys Acta Rev Cancer 1876:188549CrossRefPubMed
Metadata
Title
Efficacy of sintilimab combined with neoadjuvant chemotherapy and trastuzumab in conversional treatment of locally advanced HER2-positive gastric cancer: case analysis and literature review
Authors
Sidikjan Ibrahim
Amina Maimaitiaili
Guangsheng Zhu
Shengwei Ye
Publication date
01-12-2024
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 12/2024
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-024-06024-6

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