Terumi Tanigawa

An attempt to establish real-world databases of poly(ADP-ribose) polymerase inhibitors for advanced or recurrent epithelial ovarian cancer: the Japanese Gynecologic Oncology Group

The development of new treatments for gynecological malignancies has been conducted mainly through collaborative international phase III trials led by the United States and Europe. The survival outcomes of many gynecological malignancies have greatly improved as a result. Recent large-scale genome-wide association studies have revealed that drug efficacy and adverse event profiles are not always uniform. Thus, it is important to validate new treatment options in each country to safely and efficiently provide newly developed treatment options to patients with gynecological malignancies. The Japanese Gynecologic Oncology Group (JGOG) is conducting 5 cohort studies (JGOG 3026, 3027, 3028, 3030, and 3031) to establish real-world data (RWD) of poly(ADP-ribose) polymerase (PARP) inhibitor use in patients with advanced or recurrent epithelial ovarian cancer. The RWD constructed will be used to provide newly developed PARP inhibitors for women with advanced or recurrent ovarian cancer in a safer and more efficient manner as well as to develop further treatment options. In 2022, The JGOG, Korean Gynecologic Oncology Group, Chinese Gynecologic Cancer Society, and Taiwanese Gynecologic Oncology Group established the East Asian Gynecologic Oncology Trial Group to collaborate with East Asian countries in clinical research on gynecologic malignancies and disseminate new knowledge on gynecologic malignancies from Asia. The JGOG will conduct a collaborative integrated analysis of the RWD generated from Asian countries and disseminate real-world clinical knowledge regarding new treatment options that have been clinically implemented.

The impact of cytoreductive surgery on outcomes in high tumor burden ovarian cancer after induction of PARP inhibitors

In advanced ovarian cancer, achieving R0 resection is a critical strategy for improving prognosis. However, even with R0 resection, the prognosis of patients with a high tumor burden remains poor. This study aimed to assess whether the introduction of poly(ADP-ribose) polymerase inhibitors (PARPi) has enhanced outcomes in such cases. We retrospectively analyzed patients with International Federation of Gynecology and Obstetrics (FIGO) stage III-IV ovarian cancer treated between January 2015 and December 2021. Patients were classified into Group A (pre-PARPi introduction) and Group B (post-PARPi introduction). Complete macroscopic resection was defined as R0. Progression-free survival (PFS), stratified by the Aletti Surgical Complexity Score (Aletti_SCS), was the primary endpoint and was evaluated using Cox regression models. A total of 434 patients were included. In Group A, among those who achieved R0, the median PFS was 23.5 months for patients with high Aletti_SCS (95% confidence interval [CI]=14-30) and not reached for those with low Aletti_SCS (95% CI=30-not reached; adjusted hazard ratio [HR]=0.36, 95% CI=0.20-0.62). In Group B, the median PFS was not reached in both patients with high Aletti_SCS (95% CI=not reached-not reached) and low Aletti_SCS (95% CI=22-not reached; adjusted HR=4.98, 95% CI=1.14-21.78). Following the introduction of PARPi, there was a trend toward improved PFS in patients with a higher Aletti_SCS who underwent R0 resection. These findings suggest that R0 resection may improve prognosis even in cases with a high tumor burden in the PARPi era.

The efficacy and safety of lenvatinib plus pembrolizumab in vulnerable patients with metastatic or recurrent endometrial cancer: a single institution experience

Effective management with second-line therapy with the lenvatinib + pembrolizumab regimen for patients with advanced endometrial cancer is necessary. This retrospective study enrolled patients with endometrial cancer treated with the lenvatinib + pembrolizumab regimen. We evaluated progression-free survival (PFS), overall survival (OS), safety for patients non-eligible for the KEYNOTE775 trial, aged ≥65 years, or with ECOG performance status 1-2. Forty-five patients were analyzed: 21 (47%) were aged ˃ 65 years, 16 (36%) had performance status 1-2, and 15 (33%) were non-eligible for KEYNOTE775 trial participation. Overall, the median PFS was 8.5 months (95% confidence interval [CI] 4.6-12.4), and the median OS was 15.6 months (95% CI 9.4-NA). Median PFS was significantly shorter in patients not eligible for KEYNOTE775 participation and with performance status 1-2. The median OS was significantly shorter in patients with performance status 1-2. Grade ˃3 adverse events (AEs) occurred in 78% of patients who received the lenvatinib + pembrolizumab regimen. AEs resulted in lenvatinib dose reductions in 35 patients (78%) and lenvatinib and pembrolizumab discontinuation in 3 (7%) and 5 (11%), respectively. The median time to the first lenvatinib dose reduction was 1.5 (0.92-2.3) months in all patients and was significantly shorter in patients aged >65 years. The current regimen has favorable efficacy and manageable safety with appropriate dose reduction of lenvatinib in the real world. However, the efficacy may be inferior in patients with performance status 1 or 2, heavily treated patients, and those with organ dysfunction. The current treatment status should reflect real-world data relative to the medical environment and management.