Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer
Treatment
First-line Therapy
Recommendation 1.1
- For HER2-negative patients with gastric adenocarcinoma and PD-L1 CPS 1–5, first-line therapy with nivolumab in combination with fluoropyrimidine- and platinum-based chemotherapy may be considered on a case-by-case basis.
- For patients with gastric adenocarcinoma and PD-L1 CPS 0, first-line therapy with fluoropyrimidine- and platinum-based chemotherapy, without the addition of nivolumab, is recommended.
Recommendation 1.2
- For HER2-negative patients with esophageal or GEJ adenocarcinoma, first-line therapy with nivolumab for patients with PD-L1 CPS 1–5, or pembrolizumab for patients with PD-L1 CPS 1–10, in combination with fluoropyrimidine- and platinum-based chemotherapy, may be recommended on a case-by-case basis.
- For HER2-negative patients with gastric adenocarcinoma and PD-L1 CPS 0 or PD-L1 TPS 0%, first-line therapy with fluoropyrimidine- and platinum-based chemotherapy, without the addition of PD-1 inhibitors, is recommended.
Recommendation 1.3
- Data from the primary analysis of CheckMate 648 supports Recommendation 1.3 in patients with ESCC and PD-L1 TPS ≥1%. Additional exploratory analyses from CheckMate 648 found that 91% of patients across three study arms had PD-L1 CPS ≥1, therefore, CPS ≥1 may be used as a threshold for treatment decision-making if TPS is not available.
Recommendation 1.4
- The PD-L1 cut-offs in Recommendations 1.1 to 1.4 are based on subgroup analyses presented in included studies. All possible cut-offs have not been assessed. Therefore, optimal PD-L1 cut-offs are unknown.
- Several additional studies of immunotherapy with PD-1 inhibitors plus chemotherapy, compared to placebo plus chemotherapy have shown efficacy. However, these therapy options are not currently FDA-approved.
Recommendation 1.5
- Recommendation 1.5 is applicable irrespective of CPS or TPS levels. However, the Expert Panel notes that PD-L1 CPS was ≥1 in 87% of patients included in the KEYNOTE-811 RCT.
- HER2 positivity was defined in KEYNOTE-811 as immunohistochemistry (IHC) 3+ or IHC 2+ with positive in situ hybridization (ISH) (details of testing methodology are contained in Literature review and analysis section of the full Guideline).
- Trastuzumab plus pembrolizumab and chemotherapy is recommended based on an interim analysis showing a response benefit in the first 264 patients enrolled in KEYNOTE-811. We await the analysis of primary outcomes overall survival and progression-free survival.
Second- or Third-line Therapy
Recommendation 2.1
- Although outside the scope of this review, for patients with gastric or GEJ adenocarcinoma, trifluridine and tipiracil may be offered following progression on second-line therapy.
Recommendation 2.2
Video
Recommendation Grading
Overview
Title
Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer
Authoring Organization
American Society of Clinical Oncology
Publication Month/Year
January 4, 2023
Last Updated Month/Year
October 1, 2024
Supplemental Implementation Tools
Document Type
Guideline
Country of Publication
US
Document Objectives
The purpose of this guideline was to provide recommendations for the treatment of advanced gastroesophageal cancer that include targeted therapy and immunotherapy options in the first-line treatment setting and beyond for the overall population of patients with unresectable, incurable, metastatic gastroesophageal AC or SCC whose tumors express relevant predictive biomarkers.
Target Patient Population
Patients with advanced gastroesophageal cancer
Target Provider Population
Medical oncologists and other health care professionals
PICO Questions
Is immunotherapy or targeted therapy recommended as second-line or third-line treatment for advanced gastroesophageal AC?
Is immunotherapy or targeted therapy in combination with chemotherapy (CT) recommended as first-line treatment for advanced gastroesophageal AC or SCC for subgroups of patients who are HER2-negative and express PD-L1 as defined by TPS or CPS at cutoff levels of ≥ 1, ≥ 5, or ≥ 10?
Is immunotherapy or targeted therapy in combination with chemotherapy (CT) recommended as first-line treatment for advanced gastroesophageal AC or SCC for subgroups of patients who are HER2-negative and express PD-L1 as defined by TPS or those with HER2-positive gastric or GEJ AC?
Inclusion Criteria
Male, Female, Adult, Older adult
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Treatment
Diseases/Conditions (MeSH)
D000230 - Adenocarcinoma, D000077277 - Esophageal Squamous Cell Carcinoma
Keywords
immunotherapy, HER2, Esophageal cancer, gastric adenocarcinoma, esophageal squamous cell carcinoma, human epidermal growth factor receptor 2
Source Citation
Shah MA, Kennedy EB, Alarcon-Rozas AE, et al. Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline. J Clin Oncol. 2023 January 5. doi: 10.1200/JCO.22.02331