A 5-year review of genomic medicine in breast cancer: insights from C-CAT data on 3776 Japanese patients

In Japan, despite 5 years since CGP tests were covered by insurance in 2019, low drug accessibility rates remain a critical issue. We evaluated drug accessibility in 3776 breast cancer from the C-CAT database using two criteria: the proportion first linked to PMDA-approved drugs with phase III trial evidence for breast cancer through CGP tests but not existing Companion diagnostics [CDx] (*), and the proportion first linked to PMDA-approved drugs including based on phase I and II trial evidence (**). Additionally, cases linked to investigational drugs for non-PMDA-approved drugs were counted.

We identified the top 100 genetic alterations in Japanese breast cancer via CGP tests, listing corresponding drugs from C-CAT reports. Drug accessibility was re-evaluated through simulations with updated evidence levels by a member of the expert panel at Osaka University (EP-EL in OUH).

Results showed the proportion improved to 28.4% under the newest EP-EL in OUH, including 3.4% for HER2-negative cases eligible for HER2-targeted therapy due to ERBB2 amplification and 25.0% for ER-positive, HER2-negative cases eligible for capivasertib–fulvestrant therapy due to PIK3CA, AKT1, and PTEN alterations (*). However, in part, initial false negatives for HER2 status and practical difficulties in using CGP tests as a CDx for capivasertib exist. Including mutations like TMB-H, MSI-H, BRAF V600E mutation, and NTRK fusions raised the proportion to 37.9% (**), but lacking drugs with phase III trials evidence.

These findings highlight the ongoing difficulties in demonstrating clear clinical utility of CGP tests in Japan, emphasizing the need for broad discussions on its future direction.