Introduction/Background Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS), has been shown to be not oncologically inferior to primary debulking surgery for patients affected by advanced epithelial ovarian cancer (EOC). However, 20% of patients don’t respond and therapeutic options are limited. The genomic landscape could, at least partially, explain this phenomenon. By correlating mutational profiles with clinical outcomes, we aimed at identifying genomic features of resistance to platinum-based chemotherapy.
Methodology FPG500 (IRB 3837) is a comprehensive cancer genome profiling programme at Fondazione Policlinico Agostino Gemelli IRCCS. An evaluation of 523 genes (TSO500HT, Illumina) is provided. All EOC patients addressed to NACT and enrolled in FPG500 were included. Response to NACT was scored following the chemotherapy response score (CRS): no/minimal tumor response (CRS1), partial response (CRS2), and total response (CRS3). Age, residual tumour at IDS, and stage were also considered.
Results At data cut-off of the 9th of January 2023, 96 EOC patients were included in this preliminary analysis. 85 patients had at least one genomic alteration (78%). The overall mean of alterations was 1.75 (SD=1.37). CCNE1 amplifications were associated with older age (17% age < 64 years vs 26.5% > 64 years), and worse CRS (24% CRS 1–2 vs 15% CRS 3), similar to PIK3CA (mainly single nucleotide variants [SNVs] or insertion/deletions [Indels]) (37% CRS 1–2 vs 19% CRS 3). MYC amplifications and PIK3CA alterations were associated with a more advanced stage (respectively 37.5% and 39% stage IV vs 27% and 25% stage III). However, MYC was associated to with a better response to NACT (28% CRS 1–2 vs 42% CRS 3).
Conclusion CCNE1, MYC and PI3KCA genomic alterations seem to be associated with stages and response to chemotherapy, however, a sample size of 365 patients is required to obtain statistical significance. The enrollment is ongoing and results are expected in 2025.
Disclosures The authors declare no disclosures.
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