Gastric cancer remains a significant health burden, especially in Asia. Potassium-competitive acid blockers (P-CABs) provide stronger acid suppression than proton pump inhibitors (PPIs), but their long-term impact on metachronous gastric cancer (MGC) remains unclear. This study evaluated the incidence and duration-dependent risk of MGC in P-CAB/PPI users. This multicenter retrospective cohort study included patients from 15 institutions in Japan who underwent endoscopic or surgical resection for gastric cancer between 2014 and 2022. After exclusions, 7172 patients who had received H. pylori eradication were analyzed. Chronic use of P-CAB/PPI was defined as administration for more than 3 months. The primary outcome was the incidence of MGC. Cox regression models were used, along with subgroup analyses based on duration and initial treatment type (endoscopy versus surgery). During a median follow-up of 5.8 years, MGC developed in 342 patients. The incidence was highest among P-CAB users (20.9 per 1,000 person-years), followed by PPI users (13.5) and non-users (7.1). Both P-CAB and PPI use were independently associated with increased MGC risk (hazard ratio 3.89 and 1.75, respectively). The association between P-CAB use and MGC was stronger with longer durations of use (hazard ratio 3.44 for < 1 year, 3.95 for 1–3 years, and 9.36 for > 3 years) and was particularly evident in the post-endoscopic group (hazard ratio 4.22) in subgroup analyses. Chronic use of P-CAB/PPI were associated with MGC. Longer duration may be associated with increased risk of MGC. Further studies are warranted to validate these findings.
BACKGROUNDS:Prurigo nodularis (PN) is a chronic pruritic inflammatory disease associated with immune and neural dysregulation. Although nemolizumab has demonstrated efficacy in clinical trials, real-world post-marketing data remain limited. OBJECTIVE:To evaluate the real-world efficacy, safety, and drug survival of nemolizumab in patients with PN. MATERIALS AND METHODS:We retrospectively analyzed 38 patients with PN treated with nemolizumab at a single center. Peak Pruritus Numerical Rating Scale (PP-NRS) and Prurigo Nodularis Investigator's Global Assessment (PN-IGA) were assessed up to Week 24. Treatment-emergent adverse events (TEAEs) and drug survival were evaluated. RESULTS:Mean PP-NRS rapidly improved from 8.1 at baseline to 1.8 at Week 8 and remained stable through Week 24 (p < 0.001). PN-IGA scores gradually improved from 3.1 to 1.4 by Week 24 (p < 0.01). At Week 24, ≥4-point PP-NRS improvement and PP-NRS 0/1 were achieved in 90.9% and 59.1% of patients, respectively, while PN-IGA 0/1 was achieved in 50.0%. Early PP-NRS improvement correlated with long-term outcomes. TEAEs occurred in 39.5%, mainly cutaneous reactions, and drug survival was significantly lower in patients with TEAEs. CONCLUSION:Nemolizumab provided rapid and sustained itch relief with gradual lesion improvement in real-world PN. Early pruritus response may predict long-term efficacy, while adverse events affect treatment persistence.
Abstract Introduction: Petosemtamab, a bispecific antibody targeting LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5) and EGFR, is under clinical development. Wnt-driven LGR5, a stem cell-associated marker, stabilizes EGFR by preventing lysosomal degradation, thereby promoting cancer cell survival. However, its role in lung squamous cell carcinoma (LUSC) remains unclear. This study evaluates the impact of LGR5 expression on clinical characteristics, genomic alterations, and therapeutic outcomes in LUSC. Methods: Using the LC-SCRUM-Asia clinico-genomic database, mRNA levels of LGR5, EGFR, and other genes were assessed via the AMOY Master Panel. High LGR5 was defined as above the median. Clinical, genomic characteristics, and treatment outcomes were compared between high and low LGR5 groups. Results: LGR5 expression was evaluated in 233 LUSC patients between June 2021 and February 2022. The median LGR5 expression was 0.02 FPKM (range: 0.00-5.44), and the median EGFR expression was 12.09 FPKM (range: 0.07-572.49). No correlation was observed between LGR5 and EGFR expression (Pearson r = -0.0387, P = 0.687). Clinical characteristics, including age, sex, smoking history, ECOG-PS, and clinical stage, did not differ significantly between high and low LGR5 groups. The prevalence of driver gene alterations (KRAS mutation: 6 vs. 3, EGFR mutation: 2 vs. 4, MET ex14 skipping: 2 vs. 4, ALK fusion: 3 vs. 1) also showed no significant differences (P = 0.816). Among 103 patients receiving first-line ICI with or without chemotherapy, the median PFS was 8.0 months in the high LGR5 group and 5.6 months in the low LGR5 group (HR = 0.91, 95% CI: 0.58-1.44, P = 0.570). In 90 patients treated with first-line platinum-based chemotherapy, the median PFS was 5.5 months in the high LGR5 group and 4.3 months in the low LGR5 group (HR = 0.99, 95% CI: 0.52-1.91, P = 0.985). Wnt (P-weighted Log2FC = 0.753), Hedgehog (P-weighted Log2FC = 0.877), and Notch (P-weighted Log2FC = 0.564) pathways, key regulators of stem cell function, were significantly upregulated in the high LGR5 group (all P < 0.05). Conclusion: High LGR5 expression does not define a clinically or genomically distinct subgroup of LUSC; however, it is associated with a transcriptionally stemness-activated phenotype characterized by upregulation of Wnt, Hedgehog, and Notch pathways. These findings suggest that LGR5-high LUSC represents a biologically distinct subtype that may inform future development of LGR5×EGFR-targeted therapies. Citation Format: Yu Tanaka, Shuji Murakami, Kazumi Nishino, Motoko Tachihara, Ichiro Nakachi, Mayu Kawakami, Satoshi Hara, hitomi Aono, Shoichi Kuyama, Gaku Yamamoto, Eri Sugiyama, Tetsuya Sakai, Hiroki Izumi, Shigeki Umemura, HIBIKI UDAGAWA, Yoshitaka Zenke, Shingo Matsumoto, Kiyotaka Yoh, Koichi Goto. Clinical, genomic, and therapeutic outcomes of lung squamous cell carcinoma with high LGR5 expression : A study from the LC-SCRUM-Asia database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7919.
