Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer
Publication Date: January 5, 2023
Treatment
First-line Therapy
Recommendation 1.1
For HER2-negative patients with gastric adenocarcinoma and PD-L1 combined positive score (CPS) ≥5, first-line therapy with nivolumab in combination with fluoropyrimidine- and platinum-based chemotherapy is recommended. (EB, B, M, S)
Qualifying statements:
- 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.
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Recommendation 1.2
For HER2-negative patients with esophageal or GEJ adenocarcinoma, first-line therapy with nivolumab for patients with PD-L1 CPS ≥5, or pembrolizumab for PD-L1 CPS ≥10, in combination with fluoropyrimidine- and platinum-based chemotherapy is recommended. (EB, B, L, S)
Qualifying statements:
- 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.
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Recommendation 1.3
For patients with ESCC and PD-L1 CPS ≥10, pembrolizumab plus fluoropyrimidine- and platinum-based chemotherapy is recommended. (EB, B, H, S)
Qualifying statement:
- 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.
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Recommendation 1.4
For patients with ESCC, and PD-L1 tumor positive score (TPS) ≥1%, nivolumab plus fluoropyrimidine- and platinum-based chemotherapy, or nivolumab plus ipilimumab are recommended. (EB, B, M, S)
Qualifying statements for Recommendations 1.1 to 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.
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Recommendation 1.5
For patients with HER2-positive gastric or GEJ previously untreated, unresectable or metastatic adenocarcinoma, trastuzumab plus pembrolizumab is recommended, in combination with fluoropyrimidine- and oxaliplatin-based chemotherapy. (EB, B, L, S)
Qualifying statements:
- 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.
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Second- or Third-line Therapy
Recommendation 2.1
For patients with advanced gastroesophageal or GEJ adenocarcinoma whose disease has progressed following first-line therapy, ramucirumab plus paclitaxel is recommended. (EB, B, M, S)
Qualifying statement:
- 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.
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Recommendation 2.2
For HER2-positive patients with gastric or GEJ adenocarcinoma who have progressed following first-line therapy, trastuzumab deruxtecan is recommended. (EB, B, M, S)
Note: Although the key evidence for this recommendation includes patients who received therapy in the third-line setting, this option is FDA-approved as a second-line and later therapy option.
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Recommendation Grading
Disclaimer
Overview
Title
Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer
Authoring Organization
American Society of Clinical Oncology
Publication Month/Year
January 5, 2023
Supplemental Implementation Tools
Document Type
Guideline
Country of Publication
US
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
Supplemental Methodology Resources
Methodology
Number of Source Documents
58
Literature Search Start Date
January 1, 2010
Literature Search End Date
March 4, 2022