Trends in the needs and clinical utility of comprehensive genomic profiling test in rare cancers before and after the National Health Insurance coverage in Japan.
Authors: Sanomachi Tomomi , Okuma Hitomi Sumiyoshi , Mizuno Takaaki , Kojima Yuki , Maejima Aiko , Narita Yoshitaka , Ohe Yuichiro , Yamazaki Naoya , Kawai Akira , Okusaka Takuji , Kato Ken , Sunami Kuniko , Koyama Takafumi , Kohno Takashi , Ichikawa Hitoshi , Kakishima Hiroki , Yamamoto Noboru , Yatabe Yasushi , Yonemori Kan 
Published: June 2023

e15159

Background: Rare cancers have poor prognosis due to lack of standard and investigational treatment options. In our previous report, genomically matched therapy was performed for patients with rare cancers by comprehensive genomic profiling (CGP) test using next-generation sequencing (NGS), with some success. After CGP was covered by National Health Insurance (NHI: A system in which all citizens are covered by public health insurance) in Japan in 2019, it was expected that its needs and clinical utility would be further enhanced by the operation of CGP in the universal health insurance system, but the transition of the needs and effectiveness for CGP for rare cancers remains unclear. Methods: Patients with metastatic or unresectable solid tumors (including rare cancers defined as an incidence of less than 6/100,000/year) who agreed to NGS testing and underwent NCC Oncopanel NGS before or after NHI coverage at the National Cancer Center Hospital (Tokyo, Japan) were included. Patients' clinical background, treatment, outcome, and survival were reviewed. Patients were classified into pre-NHI coverage group (pre-group; clinical research patients: July 2013-April 2016) and post-NHI coverage group (post-group; practice patients: July 2019-July 2022) according to when they received NGS testing. Cancer types were classified into disease groups according to the WHO-proposed ICD10 classification of malignancies. Information on those who received molecularly “matched” treatment and the overall response rate were identified. All data was collected from the electronic medical records. Results: A total of 956 patients were identified; 289 in the pre-group and 667 in the post-group. Of the pre-group patients, 39% (112/289) were classified as rare cancers, most frequent being ovarian cancer, cholangiocarcinoma, and cervical cancer. Of the post-group patients, 52% (348/667) were classified as rare cancers, most frequent being malignant melanoma, cholangiocarcinoma, and cancer of unknown primary origin. Rare cancers were identified into 10 disease groups in the pre-group, while this number increased to 13 disease groups in the post-group. The most frequently altered genes in the pre-group were TP53, KRAS, and FBXW7, BRCA2 whereas those in the post-group were TP53, BRCA2, and APC. In the pre-group, 8%(9/112), in the post-group, 12% (41/348) of patients were treated with a genomically “matched” therapy and the response rates were 11% and 29% for the pre- and post-groups, which was comparable to the usefulness of CGP in the treatment of rare cancers compared to more common cancers. Conclusions: The use of CGP in the treatment of rare cancers under the national health insurance system has enabled us to expand the usage to a variety of disease groups, indicating a growing need.