For thiotepa, etoposide, IT anti-tumor drugs are a common method for treating LMD

The gap

Evidence profile

Sourced from the future work of the source papers, classified as general, drawn from work published between 2025 and 2026, spanning 3 journals. Those papers have been cited 27 times in total.

Supporting evidence — 3 representative gaps

• Innovative pathological and therapeutic approaches for poorly cohesive gastric cancer (2026) · Frontiers in Oncology · doi

  4.1 Emerging targets and therapeutic strategies In gastric cancer, novel therapeutic strategies based on combi- nation approaches are emerging. The phase II ILUSTRO study evaluated the combination of mFOLFOX6, zolbetuximab, and nivolumab, showing promising activity in patients with high CLDN18.2 expression, with an objective response rate (ORR) of 68.6% and a median progression-free survival (PFS) of 14.8 months (72). Results from the ongoing phase III LUCERNA trial are eagerly awaited; this study is investigating the addition of zolbetuximab and pembrolizumab to chemotherapy in patients with metastatic gastric cancer with high CLDN18.2 expression and PD-L1 positivity (103). In parallel, the phase III trial NCT06093425 will evaluate a similar strategy using osemitamab, a next-generation, humanized IgG1 in combination with anti-CLDN18.2 monoclonal antibody, pembrolizumab and chemotherapy as first-line treatment for ad- vanced or metastatic gastric cancer (104). Notably, this study was designed on the basis of emerging data from cohort G of the phase I/II TranStar102 study, which demonstrated a confirmed objective response rate (ORR) of 68% and a median progression-free survival (PFS) of 16.6 months (95% CI, 5.8–21.7) in patients with known CPS and high/medium CLDN18.2 expression (defined as membra- nous CLDN18.2 staining ≥2+ in ≥40% of tumor cells by central immunohistochemistry), with a manageable safety profile consis- tent with the drug class (71). In addition to CLDN18.2-directed strategies, there are also ongoing trials evaluating the combination of immunotherapy with agents targeting alternative oncogenic pathways. In this context, the phase III FORTITUDE-102 trial is evaluating nivolumab in combination with bemarituzumab in patients with FGFR2b-overexpressing gastric cancer; results are awaited (105). Another emerging target under investigation in gastric cancer is TROP2, a transmembrane glycoprotein highly expressed in several epithelial tumors and associated with tumor proliferation and poor

  generalfuture work
  Keywords: cldn gastric cancer phase emerging combination patients strategies high expression trial therapeutic zolbetuximab nivolumab objective
• A review on intrathecal administration of medications for leptomeningeal metastases in solid tumors (2025) · Frontiers in Pharmacology · cited 14× · doi

  for thiotepa, etoposide, IT anti-tumor drugs are a common method for treating LMD. IT chemotherapy drugs and targeted and immunotherapy drugs are summarized in Tables 1, 2, respectively. Based on current clinical data of antineoplastic drugs in patients with solid tumor LMD, methotrexate, thiotepa, cytarabine, and cytarabine liposomes are recommended by the ESMO (Le Rhun et al., 2023), while methotrexate, topotecan, cytarabine, pemetrexed, trastuzumab, and nivolumab are endorsed by the National Comprehensive Cancer Network for the treatment of solid tumors with LMD (Central nervous system cancers V, 2024). Meanwhile, and bevacizumab, nimotuzumab, IT pembrolizumab have also been used by researchers therapy. They may be potential IT drugs for patients with LMD from solid tumors. Although some efficacy has been achieved, the role of IT in the treatment of LMD patients with solid tumors is still controversial. Due to the short OS of patients with LMD, evaluating therapeutic addition, most immunotherapy and targeted drugs are reported as individual cases, lacking large-scale clinical trials and prospective evidence, and are less commonly used in clinical practice. Some studies have examined the effectiveness of combination IT therapy in solid cancers, such as IT administration of two anti-tumor drugs, IT therapy combined with radiotherapy, and IT therapy combined with systemic therapy (Martens et al., 2013; Pan et al., 2020), but most of the IT combination therapies we identified in the present review were case reports. Although these case reports suggested suitable efficacy and safety, these drug combinations should be validated in trials to enable large, randomized, placebo-controlled clinical clinicians to make accurate judgments concerning combination IT therapies for LMD. challenging. efficacy

  generalfuture work
  Keywords: drugs solid therapy clinical patients tumor cytarabine tumors cacy combination thiotepa anti targeted immunotherapy methotrexate
• Treatment Selection for Patients with HER2-Negative Metastatic Gastric Cancer Expressing Claudin 18.2 and PD-L1 (2025) · Cancers · cited 13× · doi

  Currently, the efficacy and safety of chemotherapy combined with zolbetuximab plus ICI for HER2-negative mGCs expressing CLDN and PD-L1 are under investigation. The ILUSTRO trial is a phase II non-randomized study comprising five cohorts, and patients with mG/GEJ cancers with high (≥75% of tumor cells) or intermediate (≥50% and <75% of tumor cells) CLDN 18.2 expression are eligible (NCT03505320). The results of cohort 3A, in which three patients were treated with zolbetuximab plus pembrolizumab as third- or later- line therapy, have been reported. No tumor response was observed, and stable disease was observed in two patients [97]. In the ongoing cohort4A/4B, patients received combination chemotherapy with mFOLFOX6, zolbetuximab, and nivolumab. The results of this cohort are anticipated [13,14,51,61]. If the trial demonstrates positive outcomes, combination chemotherapy with zolbetuximab and nivolumab may become a standard treatment for HER2-negative mGCs expressing CLDN 18.2 and PD-L1 in the future. However, this trial is ongoing, and the publication of the results is pending. The selection of treatment for this population remains an important clinical issue. Fibroblast growth factor receptor 2b (FGFR2b) is emerging as another target molecule of mGCs. FGFR2b overexpression is observed in approximately 16% of HER2-negative Cancers 2025, 17, 1120 12 of 18 mGCs [98]. Bemarituzumab is a humanized IgG1 kappa monoclonal antibody targeting the extracellular domain of FGFR2b, which inhibits downstream signaling and downregulates FGFR2b [99]. Although tyrosine kinase inhibitors targeting the fibroblast growth factor receptor family are frequently associated with hyperphosphatemia, the risk of hyperphos- phatemia is considered lower with bemarituzumab because it does not inhibit fibroblast growth factor 23 (FGF23) signaling, the ligand responsible for phosphate and vitamin D metabolism [100]. In the phase II FIGHT trial, the efficacy and safety of bemarituzumab plus mFOLFOX6 for patients with HER2-negative FGFR2b-positive mGCs were analyzed. In patients with FGFR2b-overexpressing tumors (an IHC score of 2+ or 3+ in ≥10% of tumor cells), bemarituzumab plus mFOLFOX6 significantly improved median PFS (14.0 vs. 7.3 months; HR 0.43; 95% CI 0.26–0.73) and median OS (24.7 vs. 11.1 months; HR 0.52; 95% CI 0.31–0.85) compared with mFOLFOX6 alone [101]. Several trials evaluating be- marituzumab efficacy are ongoing: the phase III FORTITUDE-101 trial (NCT05052801), phase Ib/III FORTITUDE-102 trial (NCT05111626), and phase Ib/II FORTITUDE-103 trial (NCT05322577) [102–104]. FORTITUDE-101 and FORTITUDE-103 evaluate bemarituzumab plus chemotherapy vs. placebo plus chemotherapy. FORTITUDE-102 and FORTITUDE-103 evaluate bemarituzumab and nivolumab plus chemotherapy vs. placebo and nivolumab plus mFOLFOX6. It has been reported that approximately 20% of CLDN-positive GCs are FGFR2b-positive [105]. Although the prevalence remains unclear, evidence suggests that a subset of mGCs with FGFR2b overexpression express PD-L1 CPS [106]. Since FGFR2b overexpression can overlap with CLDN 18.2 or PD-L1 CPS, treatment selection for pa- tients with HER2-negative mGC expressing multiple overlapping biomarkers could be further complicated.

  generalfuture work
  Keywords: fgfr plus trial fortitude chemotherapy mgcs patients bemarituzumab negative cldn phase mfolfox zolbetuximab tumor nivolumab

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