Kim JH, et al. J Gynecol Oncol. 2022 May;33(4):e54. https://doi.org/10.3802/jgo.2022.33.e54

Objective To investigate the prognostic value of cancer antigen 125 (CA125) related variables on progression free survival and overall survival in primary and recurrent ovarian cancers. Method A comprehensive review of the Medline, Embase, and Cochrane Library databases was conducted to identify relevant literature on survival outcomes according to the ELIMination Rate Constant K (KELIM), Gynecologic Cancer InterGroup (GCIG) CA125 response criteria, CA125 half-life, and CA125 nadir levels during first line or later line chemotherapy. The search included articles published before February 2023. Cut-off values determining the favorable/unfavorable score of each study were extracted, and pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed using a random effects model to identify the relationship between survival outcomes of the favorable/unfavorable groups, which was determined by an individual model using CA125 kinetics. Results A total of 27 studies with 14 444 patients with epithelial ovarian cancer were included in this meta-analysis. In primary ovarian cancer, a favorable KELIM score, determined by individual modeled cut-off values, was associated with a significant progression free survival (HR 0.53, 95% CI 0.45 to 0.62) and overall survival (HR 0.51, 95% CI 0.43 to 0.62) benefit in the primary setting. The favorable KELIM scored group also correlated with a better progression free survival (HR 0.54, 95% CI 0.47 to 0.62) in relapsed disease. We failed to demonstrate a better prognostic value of the GCIG response criteria and the CA125 half-life for progression free survival and overall survival. Conclusion Novel chemotherapy response scores, such as KELIM, may be more clinically relevant than other prognostic models using CA125 kinetics, being directly associated with a more favorable survival in both the primary and relapsed setting in patients with epithelial ovarian cancer. Study registration The systemic review and meta-analysis were registered in PROSPERO (CRD42023385512).

Background: The location of BRCA mutations within functional domains may affect sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapy. This study aimed to evaluate the progression-free survival (PFS) benefit from the PARP inhibitor in relation to the location of mutations in BRCA1/BRCA2 in newly diagnosed ovarian cancer. Materials and methods: Patients with advanced stage III-IV epithelial ovarian cancer who had deleterious BRCA1 or BRCA2 were analyzed. PFS and clinical and molecular data were compared between patients who received olaparib or niraparib as frontline maintenance therapy and those who did not. Subgroup analyses were conducted based on the location of BRCA mutations within the functional domain or the ovarian cancer cluster region (OCCR). Results: Of the 380 patients, 242 (63.7%) harbored BRCA1 mutation, 137 (36.1%) harbored BRCA2, and one (0.3%) harbored both BRCA1 and BRCA2. With a median follow-up of 35.8 months, the DNA binding domain in BRCA1 (HR, 0.34; 95% CI, 0.15–0.79; p = 0.01) and BRCA2 (HR, 0.25; 95% CI, 0.08–0.78; p = 0.01) demonstrated particularly significant benefit. In patients who harbored BRCA1 mutation in the C-terminal domain (BRCT), no statistically significant PFS benefit from PARP inhibitor was observed (HR, 0.76; 95% CI, 0.39–1.52; p = 0.44). PFS benefit from PARP inhibitor maintenance was observed in both OCCR (HR, 0.49; 95% CI, 0.32–0.74; p < 0.01) and non-OCCR (HR, 0.51; 95% CI, 0.27–0.63; p < 0.01). Conclusions: Frontline PARP inhibitor maintenance therapy demonstrated a significant PFS benefit in patients with BRCA1/2 mutations, with particularly pronounced benefits for those with mutations located in the DBD of BRCA1 and BRCA2. However, the benefit was less evident for patients with BRCA1 mutations located in the BRCT domain.

Ha HI, et al. J Gynecol Oncol. 2023 Dec;35(1):e31. https://doi.org/10.3802/jgo.2024.35.e31

Kim SI, et al. J Gynecol Oncol. 2022 Oct;34(1):e9. https://doi.org/10.3802/jgo.2023.34.e9

Shim H, et al. J Gynecol Oncol. 2023 Dec;35:e38. https://doi.org/10.3802/jgo.2024.35.e38