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Advanced Gastric Cancer

CE / CME

Cases and Challenges in the Optimal Treatment of Advanced Gastric Cancer

Physician Assistants/Physician Associates: 1.00 AAPA Category 1 CME credit

Nurse Practitioners: 1.00 Nursing contact hours, includes 1.00 hour of pharmacotherapy credit

Released: April 27, 2023

Expiration: April 26, 2024

Steven Maron
Steven Maron, MD
CME/CE Information

Activity

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Course Completed

Introduction

Approximately 26,500 individuals are diagnosed with GC annually in the United States, and 11,130 die of the disease.1 Many patients present with advanced disease at diagnosis because there are no effective screening methods available.2 Disease development has been linked to tobacco smoking, high-sodium diets, and uncontrolled infection with Helicobacter pylori. Other risk factors include infection with Epstein-Barr virus, and high alcohol consumption, obesity, and pernicious anemia.2,3 Between 3% and 5% of patients have germline mutations associated with GC development.3,4 Disease prevalence is highest in East Asia, Eastern Europe, and Central/South America; however, the overall incidence of GC is decreasing due to improved risk factor management and prevention strategies.2 Five-year survival across all stages of GC has improved since the 1970s, but today is only 33%. Even that is misleading, given that most patients are diagnosed with advanced disease or mGC, for whom the 5-year survival rate is only 6%.1 Studies from Japan, where diagnosis and early resection are the norm, show that with improved early diagnosis and treatment, survival outcomes can be improved.2

Depending on family history and DNA-based analyses, clinicians should maintain increased suspicion for the presence of a hereditary predisposition in GC. Patients presenting at young ages should be evaluated for hereditary diffuse GC (germline CDH1 or PALB1 mutation) or Lynch syndrome (germline mutations of DNA mismatch repair genes). Other hereditary GC syndromes include juvenile polyposis syndrome, Peutz Jeghers syndrome, and familial adenomatous polyposis.4 Referral to genetic counseling and germline DNA testing is essential for patients with a suspected hereditary predisposition for GC to confirm or rule out the diagnosis. Genetic counseling can also provide screening recommendations for patients with a hereditary predisposition for GC and their family members.4

 

Expert Insights From Dr Maron: The Importance of Assessing Family History

 

 

The recommended initial workup for patients with suspected GC includes complete personal and family history and physical examination, complete blood count and comprehensive metabolic panel, and upper gastrointestinal (GI) endoscopy and biopsy. All patients should have computed tomography (CT) with oral and intravenous contrast of the chest, abdomen, and pelvis.4 Recommended molecular testing in the setting of mGC is summarized in Table 1. All newly diagnosed patients should be evaluated for deficiency in mismatch repair genes (dMMR using immunohistochemistry (IHC) and/or microsatellite-instability status (MSI status using next-generation sequencing (NGS) or PCR. In locally advanced, recurrent, or metastatic disease, tumor HER2 status generally should be assessed using IHC ± in situ hybridization (ISH) and PD-L1 expression using IHC.4 NGS performed on either solid or circulating tumor (ct) DNA can evaluate ERBB2 amplification (for HER2 status) and other gene alterations, including MSI status, presence of an NTRK gene fusion, tumor mutation burden (TMB, RET gene fusions, and BRAF V600E muations. Recommended testing, which is essential to guiding treatment, should only be performed in patients with ECOG performance status ≤2 or Karnofsky performance status ≥60%, to ensure patients are able to withstand the rigors of treatment.4

Table 1: Molecular Testing of Metastatic Disease4

The phase III KEYNOTE-811 trial evaluated addition of the PD-L1 inhibitor pembrolizumab to the standard-of-care therapy of chemotherapy + trastuzumab for patients with newly diagnosed HER2-positive advanced GC. Which of the following outcomes was reported with the addition of pembrolizumab to standard of care vs standard of care alone from this trial?

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