An Attempt to Develop a New Treatment Strategy for Rare Refractory Gynecological Malignancies: The Japanese Gynecologic Oncology Group

Platinum-based combination chemotherapy has been a frontline therapeutic strategy for advanced ovarian cancer. Although patients with ovarian high-grade serous carcinoma (HGSC) respond well to the combination therapy, those with relatively rare histologic subtypes, such as mucinous or clear cell carcinoma of the ovary (OCCC), show resistance to platinum-based chemotherapy. Even with the recently developed maintenance therapies using molecular targeted inhibitors for ovarian cancers, such as bevacizumab or poly (ADP-ribose) polymerase (PARP) inhibitors, the prognosis of non-HGSC ovarian cancers is unsatisfactory. To overcome the limitations in the treatment of rare ovarian cancers, the Japanese Gynecologic Oncology Group (JGOG) has launched a comprehensive project utilizing publicly available genomic databases, including a national clinico-genomic database maintained by the Center for Cancer Genomics and Advanced Therapeutics (C-CAT). JGOG, a leading group in Japan that conducts clinical trials for the treatment of gynecological malignancies, also established a nationwide network through the long-standing efforts of all participants. Currently, JGOG is engaged in a phase II international clinical trial (CYH33-G201: jRCT2031210216), targeting OCCC with PIK3CA hotspot mutations. The CYH33-G201 trial is sponsor-initiated, and JGOG, in collaboration with pharmaceutical companies, is actively recruiting participants. To expand the functions of the nationwide network that JGOG had already established, we held explanatory meetings for this clinical trial in nine different areas throughout Japan to promote the penetration of the CYH33-G201 trial. Through C-CAT database analysis, we estimated that approximately 40% of the patients with OCCC harbored at least 1 of the 17 PIK3CA hotspot mutations designated in the CYH33-G201 trial. JGOG will continue the challenge of establishing novel treatment strategies for rare refractory cancers that will benefit patients suffering from gynecological malignancies, especially those who do not receive satisfactory standard treatment and care.