Will revised gastric cancer clinical guidelines address Vyloy’s diagnostic gap?
Astellas' targeted therapy for gastric cancer, Vyloy (zolbetuximab), has received the highest level of recommendation in clinical guidelines in Korea and the United States, redirecting attention to addressing the diagnostic gap for Claudin 18.2 occurring in the nation’s treatment environment.
On Monday, the revised version of the Korean Gastric Cancer Practice Guidelines (fifth edition) was published in the online version of the Journal of Gastric Cancer (JGC), the official journal of the Korean Gastric Cancer Association. The revised edition was published two years after the fourth edition was published in 2022.
The new edition focuses on systemic therapy, which has significantly changed over the past two years.
The anti-PD-1 immuno-oncology drugs Opdivo (nivolumab) and Keytruda (pembrolizumab), the Claudin 18.2-targeted therapy Vyloy, and the antibody-drug conjugate (ADC) Enhertu (trastuzumab deruxtecan) have been added as new recommendations for treating unresectable locally advanced or metastatic gastric cancer.
Opdivo (PD-L1 CPS ≥5) and Keytruda (PD-L1 CPS ≥1) in combination with conventional chemotherapy were recommended for the first-line treatment of patients who are HER2-negative and PD-L1-positive, and Keytruda in combination with conventional chemotherapy plus trastuzumab was recommended for the first-line treatment of patients who are HER2-positive and PD-L1-positive (Level of Evidence: High, Recommendation: Strong for).
For first-line treatment of patients who are HER2-negative and Claudin 18.2-positive, Vyloy in combination with chemotherapy (CAPOX or FOLFOX) was recommended (Level of Evidence: High, Grade of Recommendation: Strong for).
Cyramza (ramucirumab) in combination with paclitaxel is preferred for second-line treatment, and Enhertu was preferred for third-line treatment in HER2-positive patients (Level of Evidence: High, Grade of Recommendation: Strong for).
Including Vyloy in the Korean clinical guidelines for gastric cancer is also expected to accelerate reimbursement for Claudin 18.2 as a companion diagnostic (CDx).
Although Astellas announced the uncovered launch of Vyloy in January, Claudin 18.2 cannot be diagnosed in Korean clinics.
To prescribe Vyloy, patients must test positive for Claudin 18.2 using Roche Diagnostics' VENTANA CLDN18(43-14A) RxDx Assay, licensed as a companion diagnostic device. However, the companion diagnostic fee has not been determined, making it impossible to use the drug without treatment.
Normally, whenever a new cancer type or biomarker is added to the Immunohistochemistry (IHC) test, the new medical technology must be evaluated by the National Evidence-based Healthcare Collaborating Agency (NECA) before the Health Insurance Review and Assessment Service (HIRA) can reimburse the cost of the test. This process can take up to 15 months, leaving a diagnostic gap for Claudin 18.2.
In response, the relevant medical societies submitted an opinion letter to the HIRA emphasizing Vyloy's clinical need and that the IHC test for Claudin 18.2 is not a new medical technology. Still, HIRA has delayed its decision, demanding that Vyloy provide evidence of inclusion in Korean and international clinical guidelines.
Against this backdrop, Vyloy has met all the additional evidence required by the review panel. It was listed in the revised gastric cancer guideline (Version 5.2024) released by the U.S. National Comprehensive Cancer Network (NCCN) on Dec. 20 (Category 1) and in the Korean clinical guidelines for gastric cancer on Tuesday.
Notably, Vyloy is listed as the highest level of recommendation in the Korean and U.S. clinical guidelines, removing any doubt about its clinical utility.
In addition, both guidelines added Claudin 18.2 as a key biomarker in gastric cancer care, specifying IHC as the test of choice and emphasizing that companion diagnostics are an integral part of using Vyloy.
Industry insiders are watching with interest to see if the companion diagnosis fee for Claudin 18.2 will go directly to the HIRA’s reimbursement review at the second meeting of the Experts Evaluation Committee, which is scheduled for later this month.