Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline Update

Area of Science:

• Gastrointestinal Oncology
• Medical Oncology
• Cancer Treatment Guidelines

Background:

• Gastroesophageal cancer (GEC) encompasses a range of malignancies including adenocarcinoma and squamous cell carcinoma.
• Treatment decisions for advanced GEC are complex and evolving with new therapeutic options.

Purpose of the Study:

• To provide updated clinical practice recommendations for immunotherapy and targeted therapy in advanced GEC.
• To guide oncologists in selecting optimal treatment strategies based on patient and tumor characteristics.

Main Methods:

• A systematic review of 12 phase III randomized controlled trials was conducted.
• An Expert Panel convened by ASCO developed the clinical practice recommendations.

Main Results:

• Immunotherapy plus doublet chemotherapy is recommended for proficient mismatch repair (pMMR)/microsatellite stable (MSS) HER2-negative GEC with PD-L1 expression ≥1.
• Zolbetuximab is recommended for GEC with positive CLDN18.2 expression and PD-L1 <1.
• Trastuzumab and doublet chemotherapy, with optional pembrolizumab for PD-L1 ≥1, is recommended for pMMR/MSS HER2-positive gastric/gastroesophageal junction (GEJ) adenocarcinoma.

Conclusions:

• Timely biomarker testing (e.g., mismatch repair, PD-L1, CLDN18.2, HER2) is crucial for informing treatment decisions in advanced GEC.
• Specific recommendations are provided for first-line and second-line therapies based on biomarker status and tumor type.
• Shared decision-making is encouraged for patients with dual PD-L1 and CLDN18.2 positivity.