Importance of development of antitumor agents for platinum-resistant ovarian cancer in Japan

Among gynecologic tumors, uterine leiomyosarcoma and advanced serous ovarian cancer are the most difficult to treat.

A clinical trial conducted by Banerjee et al showed that the addition of mammalian target of rapamycin (mTOR) inhibitor vistusertib to paclitaxel did not improve clinical outcomes in patients with platinum-resistant High-Grade serous cancer (PR-HG-SC).

In Japan, the prescription of PARP inhibitors (olaparib or niraparib) for platinum-sensitive High-Grade Serous carcinoma (HG-SC) or HG-SC with pathogenic variant in BRCA1/2 is covered by health insurance. However, it has been clarified that PARP inhibitors (olaparib or niraparib) are not effective against PR-HG-SC with pathogenic variants in BRCA1/2.

From December 2019 to February 2023, new therapies for a total of 2811 patients (Ncc oncopanel: 670; F1CDx: 2141) were examined by the cancer gene panel in cancer genomic medicine at a Japanese national university. New therapies for a total of 174 cases of advanced HG-SC, i.e., PR-HG-SC in Japanese patients were tested by cancer genomic panels. As a result of the cancer genome test, the mTOR pathogenic variants were detected in 34 PR-HG-SC cases, the PI3K pathogenic variants were detected in 11 PR-HG-SC cases, the BRCA1/2 pathogenic variants were detected in 23 PR-HG-SC cases, the HRD-related factors pathogenic variants were detected in12 PR-HG-SC cases.

Therefore, PI3K-mTOR signal inhibitors (Everolimus etc.) were orally administered to 34 PR-HG-SC cases with mTOR pathogenic variant and 11 PR-HG-SC cases with PI3K pathogenic variant. Unfortunately, no antitumor effect of Everolimus was observed in all patients (45 cases). Based on the results of this clinical trial in Japan, Japan's Ministry of Health, Labor and Welfare Pharmaceuticals Officers do not recommend or propose the use of PI3K-mTOR signaling inhibitors for PR-HG-SC. The results of the clinical trial conducted in Japan were similar to the results of the clinical trial conducted by Banerjee et al. The development of antitumor agents that are effective against PR-HG-SC is an important issue in the treatment of gynecologic malignancies.

Doctor specializing in cancer care.
Doctor specializing in emerging infectious diseases.

Manuscript Published in JAMA Oncology on March 24, 2023 by Kyoto@takumah