Clinical Report: Influence of Metastatic Sites and Histological Subtypes on PD-(L)1

Overview

This meta-analysis evaluates the impact of metastatic sites and histological subtypes on survival outcomes in HER2-negative advanced gastric and gastroesophageal cancer treated with PD-(L)1 inhibitors. The findings are based on the analysis of overall survival outcomes in various patient subgroups.

Background

Gastric cancer is a leading cause of cancer-related deaths globally, with advanced stages often resulting in poor prognosis. The introduction of PD-(L)1 inhibitors has been evaluated for their role in treatment outcomes, with responses varying based on tumor biology and metastatic patterns.

Data Highlights

Key Findings

• Overall survival improved significantly with PD-(L)1 inhibitor plus chemotherapy compared to chemotherapy alone (HR 0.79).
• Patients with liver metastases showed better survival outcomes (HR 0.75) compared to those with peritoneal metastases (HR 0.93).
• Intestinal-type tumors had a greater overall survival benefit than diffuse-type tumors (HR 0.78 vs 0.87).
• PD-L1 CPS ≥5 was associated with superior overall survival benefit (HR 0.70).
• Grade ≥3 adverse events were infrequent and primarily hematologic.

Clinical Implications

The findings suggest that treatment strategies for HER2-negative advanced gastric and gastroesophageal cancer should consider both the metastatic site and histological subtype. Specifically, patients with intestinal-type tumors and those without peritoneal metastases may derive greater benefit from PD-(L)1 inhibitor-based therapies.

Conclusion

First-line chemoimmunotherapy has been shown to prolong survival in HER2-negative gastric and gastroesophageal junction cancers.

Related Resources & Content

1. Gastric Cancer — Variability in Predictive Biomarker Expression in Gastric and Esophagogastric Junction Carcinomas Associated with Peritoneal Metastasis
2. Journal of Gastroenterology — The Role of Intratumoral HER2 Variability in Influencing Trastuzumab Effectiveness for Patients with HER2-Positive Gastric Cancer
3. Gastric Cancer — Significance of PD-1 Expressing CD8 T-Cells in the Context of Gastric Cancer
4. Gastric Cancer — Enhanced Scoring of PD-L1 in Gastric Carcinoma
5. Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline Update | Journal of Clinical Oncology
6. First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial | Journal of Clinical Oncology
7. PD-L1 CPS in gastroesophageal cancer: differences in routine care versus Checkmate 649 and implications for biopsy-site choice and assay standardisation | British Journal of Cancer
8. Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline Update | Journal of Clinical Oncology
9. First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial | Journal of Clinical Oncology
10. PD-L1 CPS in gastroesophageal cancer: differences in routine care versus Checkmate 649 and implications for biopsy-site choice and assay standardisation | British Journal of Cancer