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1114 Detection of minimal residual disease using circulating tumor DNA in patients treated with long-term PARP inhibitors maintenance for epithelial ovarian cancer
  1. Dahye Lee1,
  2. Yoo-Na Kim1,
  3. DongJu Won2,
  4. Saeam Shin2,
  5. Sang Wun Kim1 and
  6. Jung-Yun Lee1
  1. 1Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, South Korea
  2. 2Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea


Introduction/Background This study aimed to address the challenge of determining the endpoint for maintenance therapy with Poly-ADP ribose polymerase inhibitors (PARPi) in epithelial ovarian cancer (EOC) by monitoring minimal residual disease (MRD) using circulating tumor DNA (ctDNA).

Methodology A prospective observational study was conducted at a single center, involving 27 patients with EOC who underwent PARPi as maintenance therapy for at least two years. Whole blood samples were collected, and ctDNA was enriched using a custom panel targeting nine ovarian cancer-related genes (Dxome, Seoul, Korea). Sequencing with NovaSeq 6000 System (Illumina, CA, USA) and analysis with PiSeq algorithm (Dxome) were performed to assess post-treatment MRD correlated with personalized tumor next-g eneration sequencing (NGS) results. Surveillance for relapse included radiologic features from computed tomography and CA-125 levels.

Results Of the 27 patients, most had advanced-stage disease (92.6%) and high-grade serous histology (100%). PARPi was administered as front-line maintenance in 40.7% and beyond the first line in 59.3%. During a median monitoring duration of 10 months, two patients (7.4%) were MRD positive, with one showing a concordant ctDNA-based mutation and another acquiring a new mutation. Among the 92.6% MRD-negative patients, three experienced disease progression after a median of 8 months.

Conclusion CtDNA emerges as a potential biomarker for MRD monitoring in EOC patients undergoing PARPi maintenance therapy. The detection of MRD-positive cases highlights the importance of vigilant monitoring for potential relapse. CtDNA could aid in deciding whether to continue or discontinue PARPi maintenance therapy. Further research is crucial to validate the effectiveness of ctDNA in this context.

Disclosures Consulting/advisory board to AstraZeneca, CanariaBio, Eisai, Genmab, GI Innovation, ImmunoGen, MSD, and Seagen.

Funded research from Advenchen, Ascendis Pharma, Alkermes, AstraZeneca, BeiGene, BerGenBio, BMS, CanariaBio, Cellid, Clovis Oncology, Eisai, Genmab, GII, GSK, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, ONO, Regeneron, Roche, Seagen, Sutro, Synthon, and Takeda.

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