Real-world clinical utility of cancer genomic profiling tests confirmed by the National Cancer Center and Keio University

Project Researcher Yuki Saito and Chief Keisuke Kataoka (also Professor at Keio University School of Medicine) from the Division of Molecular Oncology at the National Cancer Center Research Institute, together with Senior Assistant Professor Kenro Hirata, Associate Professor Takeru Funakoshi, and their colleagues from Keio University School of Medicine, announced on January 8 that they have clarified the clinical utility of cancer genomic profiling tests in solid tumors conducted under insurance coverage. By analyzing clinical data from more than 50,000 solid tumor cases, they confirmed that patient prognosis improved with both approved and unapproved (in Japan) targeted therapies that have demonstrated efficacy. They also found that the efficacy of immune checkpoint inhibitors varies by cancer type. Their results were published in Nature Medicine on January 6.

With recent advances in cancer genomics research, numerous genetic alterations that promote carcinogenesis have been identified, molecular targeted drugs aimed at individual genetic alterations have been developed, and personalized cancer medicine is being implemented. Furthermore, "cancer genomic profiling tests" that can examine more than 100 genetic alterations simultaneously have recently become available. Since June 2019, cancer genomic profiling tests have been covered by insurance for cases meeting any of the following criteria: solid tumors for which standard treatment has been completed, or solid tumors with local progression or metastasis for which standard treatment has been completed. In addition, molecular targeted drugs may be selected using companion diagnostics prior to cancer genomic profiling tests.

However, there has been no clear detailed information on cancer genomic profiling tests, including whether the implementation of the tests actually leads to the administration of targeted therapies or unapproved drugs and improved prognosis.

Therefore, the research group examined 54,185 cases that underwent cancer genomic profiling tests covered by insurance for solid tumors in Japan between June 2019 and June 2024. These cases are from the nationwide clinical data accumulated by the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) of the National Cancer Center.

First, they examined the proportion of cases at each evidence level, indicating the strength of scientific evidence for recommending targeted therapy to patients.

The results, in descending order of expected efficacy, were: (A1) domestically approved drugs available, 11.2%; (A2) no domestically approved drugs but FDA (United States) approved drugs available (described in guidelines), 5.2%; (B) credible clinical trials/meta-analyses with expert consensus, 8.1%; (C) domestically or FDA approved drugs in other cancer types, or credible clinical trials/meta-analyses with expert consensus in other cancer types, etc., 47.4%; (D) usefulness reported in case reports, 0.6%; and (E) usefulness reported in preclinical trials, 17.5%.

When patient prognosis was compared according to these treatment evidence levels, it was favorable in the order of A1, A2, and B, while C through E showed poor prognosis. This trend was consistent not only in analyses across all cancer types but also in analyses for individual cancer types.

Next, when the researchers examined the rate of detecting genetic alterations through cancer genomic profiling tests, they found that genetic alterations targetable for treatment were detected in 72.7% of cases. On the other hand, only 8.0% had standard treatment initiated for the first time through this test. This low percentage is not necessarily problematic, as targeted therapy may be initiated through companion diagnostics, or therapeutic drugs may not exist in the first place. In fact, the rate of targeted therapy initiation, when compared by test implementation period, showed an increasing trend, reaching approximately 10% in 2023-2024, reflecting progress in the development and approval of new targeted therapeutics and the expansion of treatment options.

Additionally, when examining the rate of standard treatment initiation by cancer type, the group found significant differences in the proportion of targeted therapy initiation depending on the cancer type.

Finally, they conducted a detailed analysis of survival prognosis and response to targeted therapy in cases that underwent cancer genomic profiling tests.

As a result, they found that while the immune checkpoint inhibitor (pembrolizumab) is approved for solid tumors in general when a high tumor mutational burden (10 mutations/Mb or higher) is detected by cancer genomic profiling tests. It is effective for many cancer types, but is exceptionally ineffective for "extramammary Paget's disease." Furthermore, when comparing differences in mutational burden, they also revealed that the response rate was higher at 20 mutations/Mb or higher than at 10 mutations/Mb or higher.

The researchers also found that there were multiple cases where genetic alterations were detected by cancer genomic profiling tests and were positive, even when companion diagnostics were negative.

Saito commented: "In the future, we would like to proceed with analyses of cancer genomic profiling tests for cancers other than solid tumors, such as hematologic malignancies, and of the use of blood samples called liquid biopsy."

Journal Information
Publication: Nature Medicine
Title: Real-world clinical utility of comprehensive genomic profiling in advanced solid tumors
DOI: 10.1038/s41591-025-04086-8