We report here for the first time the initial assessment of the utility of CGP testing for patients with metastatic breast cancer under Japanese universal health insurance system. In the first 18 months after implementation of reimbursement for CGP tests, 310 CGP tests were conducted in our institute during the study period. Thirty-seven patients with metastatic breast cancer were tested, followed by pancreatic cancer and colorectal cancer. Actionable gene mutations were detected in 30 patients (85.7%), and participation in a clinical trial was recommended to 7 patients (20.0%). The drug was administered to only 2 patients (5.7%), as 3 patients (8.6%) had newly suspected germline pathological variants, and the results were subject to disclosure.
As for the current status of CGP testing under universal health insurance in Japan, 805 patients underwent CGP testing between June and October 2019, and it was reported that 10.9% of these patients were then treated based on their gene mutations (15). Furthermore, according to a report from 11 core hospitals for cancer genomic medicine, among the 747 cases in which CGP tests were conducted (from June 2019 to January 2020), 28 patients (3.7%) received genome-matched treatment (16). However, of these 28 patients treated according to their gene mutations, only 2 patients had breast cancer, and both were treated with an mTOR inhibitor for a PIK3CA mutation in that study (16). As such, under national health insurance in Japan, only approximately 10% of the patients who underwent CGP testing received a therapeutic drug targeted to their gene mutations.
This study identified several important issues regarding CGP testing under Japanese universal insurance system. The first issue is the low rate of drug accessibility due to disease progression after CGP testing. The second issue is that approximately 8% of patients died due to disease progression before the test results were disclosed; thus, the results of the CGP tests could not be explained.
Possible causes of these issues include the indication and official pricing system of reimbursement of CGP testing covered by Japanese universal health insurance system. The indication for CGP testing covered by insurance in Japan is restricted to patients with advanced solid tumors exhibiting disease progression during standard therapy (including those expected to be completed) or patients for whom there are no appropriate standard treatments, including those with rare cancers and carcinoma of unknown primary origin (8–10). Furthermore, reimbursement for the cost of a CGP test is 560,000 yen, paid in two steps. The first reimbursement is 80,000 yen after applying for the informed consent for CGP testing and preparation of tumor samples. The second reimbursement of 480,000 yen is paid when the patient receives an explanation of the CGP test results after assessment by the molecular tumor board.
In our study, new treatment options, such as those available in clinical trials, were recommended to 7 patients (20.0%) by the molecular tumor board. However, 5 (14.3%) of these patients were unable to undergo genome-matched treatment due to disease progression after the CGP test. Although the definition of the standard treatment for metastatic breast cancer prior to CGP testing remains controversial, the treatments strongly recommended in the guidelines of the Japanese Breast Cancer Society are considered candidates in Japan (17). However, the patient may be eligible for CGP testing without all standard therapies, depending on the efficacy and safety of previous therapies, the patient’s general condition, and patient preference in consideration of the 6- to 8-week turnaround time from submission of tumor tissue to return of analysis results. Therefore, our results suggest that CGP testing conducted at the appropriate time and based on the efficacy of previous therapy, the patient’s general condition, and patient preference might improve the drug accessibility rate.
As mentioned above, CGP testing is currently restricted to patients who finished standard therapies in order to avoid unnecessary investigations and reduce the burden for the molecular tumor board. However, patients who finished standard therapies for metastatic or recurrent cancer tend to have poor prognosis due to disease progression. Therefore, it is important to perform the CGP test at the diagnosis of metastatic breast cancer. Also, changes to the insurance system should be considered, in addition to increasing the number of clinical trials and promoting efforts to standardize quality while reducing the burden on the molecular tumor board.
In summary, it has been almost 2 years since CGP testing covered by the universal health insurance system was first introduced in Japan, and implementation of cancer genomic medicine is progressing. We reported here the initial assessment of CGP testing for patients with metastatic breast cancer and revealed that the percentage of patients who could reach clinical trials is low. In our sample group, a number of patients died before the test results were disclosed, although more than 80% of the patients had actionable mutations. In order to make CGP testing clinically valuable for patients with metastatic breast cancer, it will be necessary to solve problems associated with the current program of insurance coverage for CGP testing in Japan.