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PRaG Therapy of Refractory Metastatic Gastric Cancer: A Case Report.

ABSTRACT: Patients with metastatic gastric cancer had limited treatments and often had a somber prognosis, especially when patients were unable to tolerate high-intensity cytotoxic treatment due to poor physical condition or organ dysfunction after the failure of standard therapy. Here, we reported a metastatic and proficient mismatch repair (pMMR) gastric adenocarcinoma patient with the Eastern Cooperative Oncology Group (ECOG) performance status score of 2 associated with hypoproteinemia and fatigue, and poor appetite that was unable to tolerate high-intensity therapy after several chemotherapy regimens and anti-angiogenic therapy. After receiving novel triple-combination therapy, which consists of PD-1 inhibitor, Radiotherapy and Granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy (PRaG for short), the patient achieved a complete response (CR) with a progression-free survival time of 14 months, and ECOG performance status score improved from 2 to 0. A significant systemic effect was observed in this case and the PRaG triple-combination therapy might provide a novel treatment strategy for metastatic pMMR gastric cancer patients.

SUBMITTER: Xu H

PROVIDER: S-EPMC9300850 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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PRaG Therapy of Refractory Metastatic Gastric Cancer: A Case Report.

Xu Hong H Hong Zhihui Z Xu Meiling M Kong Yuehong Y Ma Yifu Y Shan Chanchan C Xing Pengfei P Zhang Liyuan L

Frontiers in immunology 20220707

Patients with metastatic gastric cancer had limited treatments and often had a somber prognosis, especially when patients were unable to tolerate high-intensity cytotoxic treatment due to poor physical condition or organ dysfunction after the failure of standard therapy. Here, we reported a metastatic and proficient mismatch repair (pMMR) gastric adenocarcinoma patient with the Eastern Cooperative Oncology Group (ECOG) performance status score of 2 associated with hypoproteinemia and fatigue, an ...[more]

PMID: 35874658

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Project description:BackgroundGastric cancer remains one of the deadliest malignancies in the world, thus urgently requiring effective and safe therapeutics. Claudin18.2 is a member of the tight junction protein family specifically expressed in gastric cancer cells. Monoclonal antibodies targeting Claudin18.2 have been receiving increasing attention recently. ASKB589 is a humanized monoclonal antibody targeting Claudin18.2.Case presentationThis case described a 65-year-old Chinese man diagnosed with gastric cancer metastasizing to the liver and multiple lymph nodes. The biomarker examination revealed that he had proficient mismatch repair (pMMR), human epidermal growth factor receptor 2 (HER2) was negative, and the combined proportion score (CPS) of PD-L1 (22C3) was 1. After being proven to be moderately positive for Claudin18.2 expression, he received ASKB589 and CAPOX (oxaliplatin and capecitabine) chemotherapy. After a six-cycle therapy (from 14 July 2022 to 29 November 2022), the target tumor was evaluated for partial response (PR) by the investigator based on the enhanced CT scan according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. However, this patient also suffered from intolerable ascites that gradually aggravated during the therapy, which was not controlled well by the supporting therapy. Therefore, the patient stopped receiving the combined therapy in our hospital and did not receive any other anti-tumor treatment. After 4 months of discontinuation of the drug, the patient's ascites almost disappeared, while the tumor continued to reduce and almost achieved clinically complete relapse (cCR). His progression-free survival (PFS) reached at least 10 months.ConclusionThis is the first case of severe ascites reported after anti-Claudin18.2 monoclonal antibody treatment for advanced gastric cancer. At the same time, the patient still benefited significantly from this incomplete treatment even after discontinuation of the drug and the PFS reached at least 10 months. The ascites might be an immune adverse effect related to the monoclonal antibody-induced antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Further mechanisms remain to be investigated.

Project description:BackgroundAnti-epidermal growth factor receptor (EGFR) therapies are important targeted agents in the treatment of metastatic colorectal cancer (CRC). However, clinical benefit is limited to patients with left-sided primary tumors and RAS wild-type (WT) disease. In right-sided chemo-refractory settings, response to anti-EGFR therapy has not been reported to date.Case descriptionWe present a case of a 70-year-old man with metachronous metastatic ascending colon adenocarcinoma who experienced an exceptional response to FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus panitumumab after failing multiple lines of therapy. He was initially diagnosed with stage IIIB (pT4aN1M0) disease and underwent hemicolectomy followed by adjuvant FOLFOX (fluorouracil, leucovorin, and oxaliplatin). Nine months after completion of adjuvant therapy, disease recurred in the liver, peritoneum, and mesenteric lymph nodes. Subsequent treatments included FOLFIRI plus bevacizumab and FOLFOX with eventual progression. Tumor genomic profiling revealed RAS/RAF WT disease, and in the absence of anti-EGFR therapy resistance mutations, the patient was offered treatment with FOLFIRI plus panitumumab. He achieved immediate palliation of his abdominal pain after one cycle, followed by normalization of his tumor markers and significant tumor regression of his hepatic, peritoneal, lung, and distant lymph node metastases within four cycles.ConclusionsTreatment options for right-sided RAS-WT metastatic CRC are limited, particularly after progression on standard chemotherapies. While anti-EGFR antibodies have demonstrated detrimental survival impact in the first-line setting for right-sided CRC, their performance in later lines is less well-characterized. This case challenges the notion of right-sided disease as uniformly resistant to EGFR inhibition and highlights the need for additional biomarker studies to identify the subset of right-sided CRC that may benefit from EGFR targeted strategies. Emerging evidence suggests that more stringent genomic criteria for EGFR resistance, beyond RAS mutation status alone, may refine patient selection for benefit from anti-EGFR therapies.

Dataset Information

PRaG Therapy of Refractory Metastatic Gastric Cancer: A Case Report.

Publications

PRaG Therapy of Refractory Metastatic Gastric Cancer: A Case Report.

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