Ki67 as a Predictor of Response to PARP Inhibitors in Platinum Sensitive BRCA Wild Type Ovarian Cancer: The MITO 37 Retrospective Study

Simple Summary Low cost, reliable predictors of benefit from PARP inhibitors (PARPi) are missing for relapsed BRCA wild-type (WT) ovarian cancer (OC). MITO 37 is a multicenter retrospective study aiming at correlating Ki67 expression at diagnosis with a clinical outcome following platinum treatment and PARPi maintenance. Clinical data were collected from 150 patients with high grade serous or endometroid BRCA WT OC treated with niraparib or rucaparib maintenance in 15 centers within MITO group. Ki67 expression was assessed by certified pathologists on tumor tissue at diagnosis and median Ki67 was used as cut-off. 136 patients were included. Median Ki67 was 45.7% (range 1.0-99.9). No statistically significant differences in response to PARPi neither in progression free survival and overall survival were identified between low and high Ki67 subgroups. High Ki-67 at diagnosis cannot discriminate responders to PARPi among OC BRCA WT patients. Background: There is compelling need for novel biomarkers to predict response to PARP inhibitors (PARPi) in BRCA wild-type (WT) ovarian cancer (OC). Methods: MITO 37 is a multicenter retrospective study aiming at correlating Ki67 expression at diagnosis with a clinical outcome following platinum treatment and PARPi maintenance. Clinical data were collected from high grade serous or endometroid BRCAWT OC treated with niraparib or rucaparib maintenance between 2010-2021 in 15 centers. Ki67 expression was assessed locally by certified pathologists on formalin-fixed paraffin embedded (FFPE) tissues. Median Ki67 was used as a cut-off. Results: A total of 136 patients were eligible and included in the analysis. Median Ki67 was 45.7% (range 1.0-99.9). The best response to platinum according to median Ki67 was 26.5% vs. 39.7% complete response (CR), 69.1% vs. 58.8% partial response (PR), 4.4% vs. 1.5% stable disease (SD). The best response to PARPi according to median Ki67 was 19.1% vs. 36.8% CR, 26.5% vs. 26.5% PR, 26.5 vs. 25% SD, 27.9% vs. 16.2% progressive disease (PD). No statistically significant differences in progression free survival (PFS) and overall survival (OS) were identified between low and high Ki67. PFS and OS are in line with registration trials. Conclusions: Ki67 at diagnosis did not discriminate responders to PARPi.

Automated summary

The expression of Ki67 at diagnosis does not predict the response to PARP inhibitors in BRCA wild-type ovarian cancer patients.