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Abstract Background Ovarian clear cell carcinoma (OCCC) accounts for 5-20% of all epithelail ovarian cancers, and is associated high recurrence rate and chemoresistance. There are some new therapies available in recent years, including bevacizumab, an anti-VEGF monoclonal antibody, and the poly ADP-ribose polymerase (PARP) inhibitors. Previous research and current support the use of both medication in OCCC. However, most of the studies reported results for all subtypes collectively in which OCCC only accounted for a small proportion of the study cohort. Besides, dislike the high-grade serous subtype, only around 10% of OCCC respond to poly ADP-ribose polymerase (PARP) inhibitor. In the subgroup analysis from ICON7, Bevacizumab had limited role in OCCC patients, in which OCCC of any stage were included. On the other hand, another 2 multi-center studies evaluated Bevacizumab as the front-line or salvage therapy revealed positive results. However, the results could be biased due to unadjusted confounders. Objective: To find the real effect of Bevacizumab on advanced stage OCCC. Materials and Methods: A systematic review via searching the Pubmed with "ovarian clear cell carcinoma" and "bevacizumab" was performed. Any comparative study met the inclusion criteria. The data were extracted, evaluated and classified by their combination of potential confounders. Primary data from National Taiwan University Hospital (NTUH) Database were collected and incorporated into the traditional meta-analysis, and the network meta-analysis. The potential confounders for analysis include "residual tumor", "FIGO stage", and "functional status". Results: There were 3 retrospective studies, including one single-center study from Japan (N=28), one multi-center study from Japan (N=145), and one multi-center study from Korea (N=138). There were 64 patients identified from NTUH database between 2011 and 2020. By traditional meta-analysis, it revealed Bevacizumab is associated with improved progression-free survival (HR 0. 62, 95% C. I. 0. 44 - 0. 87, common effect model, I2= 50%). After adjusted for confonders and analyzed by network meta-analysis, however, only "no residual tumor" is associated with improved progression-free survival (HR 0. 37, 95% C. I. 0. 14 - 0. 97). The role of Bevacizumab on OCCC is limited (HR 1. 20, 95% C. I. 0. 51 - 2. 83). Conclusion: By adjusting for possible confounders in published studies, it reveals that Bevacizumab may not improve progression-free survival in advanced-stage OCCC from a network meta-analysis. Citation Format: Fisher Kuan-Ju Huang. The unconfounded effect of bevacizumab on advanced ovarian clear cell carcinoma: a systematic review, traditional meta-analysis, and network meta-analysis abstract. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84 (5 Suppl₂): Abstract nr B056.
Fisher Kuan-Ju Huang (Mon,) studied this question.