Abstract Gastric cancer (GC) is one of the most common malignancies worldwide. Most patients are diagnosed at advanced stages due to the subtle symptoms of earlier disease and the low rate of regular screening. Systemic therapies for GC, including chemotherapy, targeted therapy and immunotherapy, have evolved significantly in the past few years. For resectable GC, perioperative chemotherapy has become the standard treatment. Ongoing investigations are exploring the potential benefits of targeted therapy or immunotherapy in the perioperative or adjuvant setting. For metastatic disease, there have been notable advancements in immunotherapy and biomarker-directed therapies recently. Classification based on molecular biomarkers, such as programmed cell death ligand 1 (PD-L1), microsatellite instability (MSI), and human epidermal growth factor receptor 2 (HER2), provides an opportunity to differentiate patients who may benefit from immunotherapy or targeted therapy. Molecular diagnostic techniques have facilitated the characterization of GC genetic profiles and the identification of new potential molecular targets. This review systematically summarizes the main research progress in systemic treatment for GC, discusses current individualized strategies and presents future perspectives. 

/pdf/gastric-cancer-treatment-recent-progress-and-future-89bjetd0.pdf

Gastric cancer treatment: recent progress and future perspectives

Rationale: Most Chinese patients with locally advanced gastric cancer at diagnosis have an overall 5-year survival rate of <50%. Surgical resection alone is not suitable for patients with locally advanced gastric cancer. Currently, comprehensive treatment is the focus of locally advanced gastric cancer. Patients concerns: The patient, a 56-year-old female, was admitted to the hospital because of “4 + months of double hydronephrosis found during a physical examination.” Who was admitted for computer tomography and gastroscopy examinations, and take pathological tissue specimens during endoscopic examination. Diagnoses: Computed tomography assessment indicated ulcerative gastric cancer with an abdominal implant, bladder, and bone metastases. An endoscopic examination revealed that the ulcer of the gastric angle was huge, and through relevant auxiliary examinations, the diagnosis of this disease is gastric cancer complicated with multiple metastases to bladder, rectum, lumbar spine, and peritoneum. Clinically diagnosed as cT4bN3M1. Interventions: The patient is currently undergoing first, second, and third line neoadjuvant therapy, combined with immunotherapy, targeted therapy, neoadjuvant intraperitoneal systemic chemotherapy, nutritional support, and other treatment plans. Outcomes: After 15 cycles of treatment, the progression-free survival had reached 15 months. The patient had an NRS2002 score of 1, an ECOG score of I, a quality of life score of 55, albumin of 35.27 g/L, and a decrease in abdominal and pelvic fluid accumulation and exudation compared to before. Lessons: We demonstrated high survival of almost 3 years in a patient with gastric cancer that was complicated by bone, peritoneal, rectal, and bladder metastases. The combination of immunotherapy, targeted therapy, and neoadjuvant intraperitoneal systemic chemotherapy, along with the maintenance of nutritional status and CTCs could be a valuable modality for the subsequent treatment and observation of similar patients.

Long-term survival in a patient with multiple metastatic gastric cancer treated with PTX plus emvolimab and disitamab vedotin: case report and treatment experience: A case report

Background Human epidermal growth factor receptor 2 (HER2) gene amplification in lung adenocarcinoma is associated with aggressive tumor behavior and poor prognosis. Currently, there is no standard targeted therapy for HER2-amplified lung cancer. Case summary A 60-year-old male presented with a mass in the right cervical spine area. Imaging and pathological examinations confirmed stage IV (T4N3M1) lung adenocarcinoma with metastases to both lungs, multiple lymph nodes, the pleura, the left adrenal gland, and the meninges. Genetic testing revealed HER2 gene amplification and low programmed death-ligand 1 (PD-L1) expression (tumor proportion score &amp;lt;1%). The patient declined conventional chemotherapy due to concerns about side effects. With his informed consent, he was treated with a combination of cadonilimab (a PD-1/cytotoxic T-lymphocyte antigen 4 bispecific antibody) and disitamab vedotin (an anti-HER2 antibody–drug conjugate), administered intravenously every 3 weeks. After nine treatment cycles over 6 months, imaging assessments showed complete disappearance of the pulmonary lesions, and the achieved complete response (CR) persisted for at least 7 months. The treatment was well-tolerated, and the patient maintained an excellent performance status (Eastern Cooperative Oncology Group score of 0) without significant adverse effects. Conclusion Treatment with cadonilimab and disitamab vedotin induced a sustained complete response in a patient with advanced HER2-amplified lung adenocarcinoma who declined chemotherapy. Thus, this combination therapy may offer a promising, effective, and well-tolerated treatment alternative for similar patients. Further clinical trials are warranted to validate these findings and potentially establish a new standard of care for this subset of lung cancer patients. 

pdf/complete-response-of-advanced-her2-amplified-lung-kcq11c4b2l99.pdf

Complete response of advanced HER2-amplified lung adenocarcinoma to cadonilimab combined with disitamab vedotin: a case report

Several clinical trials have demonstrated that chemotherapy contributes to prolonged survival in patients with previously treated advanced gastric cancer (AGC). Currently, cytotoxic agents with established efficacy for previously treated AGC include paclitaxel (PTX), irinotecan (IRI), and trifluridine/tipiracil (FTD/TPI), while the anti-vascular endothelial growth factor(VEGF) agent ramucirumab (RAM) has also shown efficacy. Pembrolizumab is indicated for AGC with microsatellite instability-high (MSI-H) or high tumor mutational burden (TMB). For human epidermal growth factor receptor 2 (HER2)-positive previously treated AGC, trastuzumab deruxtecan (T-DXd) has emerged as the first molecular targeted therapy. Additionally, claudin-18 isoform 2 (CLDN18.2)-targeting antibody therapy has been established as a first-line treatment, with numerous ongoing clinical trials in later-line settings. Other promising molecular targets include trophoblast cell surface antigen 2 (TROP2), cytoplasmic activation/proliferation-associated protein 1(CAPRIN-1), and KRAS. Furthermore, innovative therapeutic approaches such as antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), and chimeric antigen receptor T-cell (CAR-T) therapy are being developed. This review summarizes the historical and established evidence from clinical trials on previously treated AGC and discusses ongoing clinical trials and future perspectives in treatment development, with a focus on targeted therapies. Biomarker-driven treatment is expected to become the mainstream approach in the future. 

Pharmacotherapy for previously treated gastric cancer patients: current options and future developments

Abstract Currently, effective therapies for advanced gastric cancer with systemic metastasis are lacking. Pharmacological research has been slowly progressing over the past decades. Here, we report the case of a 56-year-old female with human epidermal growth factor receptor 2 (HER2) expression (IHC 2+/FISH-) in gastric cancer with systemic metastasis. The first-line therapeutic regime consisted of systemic administration of camrelizumab, local arterial infusion of oxaliplatin and arterial embolization, oral apatinib, and PS scheme (oral tegafur-gimeracil-oteracil (S-1) and paclitaxel (PTX), which was administered both intraperitoneally and systemically). After the treatment, a 3-month progression-free survival (PFS) was observed. Due to the occurrence of CTCAE grade 4 adverse reactions, the patient could not tolerate chemotherapy. In the second line of treatment, we replaced the PS scheme with disitamab vedotin and continued the use of carrilizumab and apatinib. After four cycles, efficacy evaluation showed that it was stable disease (SD), only CTCAE 1/2 grade adverse reactions occurred, and endoscopy examination showed local tumor control with a reduction in the ulcer lesion. At the time of submission of the current manuscript, a 6-month PFS was achieved and the treatment was continued. Due to the safety and efficacy of disitamab vedotin observed in our case, we propose that disitamab vedotin could be a promising drug for the treatment of advanced gastric cancer patients with HER2 expression.

Efficacy of Disitamab Vedotin in Treating HER2 2+/FISH- Gastric Cancer

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Efficacy of Disitamab Vedotin in Treating HER2 2+/FISH- Gastric Cancer