Abstract Background. Circulating tumor DNA (ctDNA) may offer a non-invasive means to evaluate tumor response and to anticipate disease dynamics before radiological changes in advanced endometrial carcinoma (EC). Methods. This ancillary analysis included patients from the multicenter, randomized, phase II, GINECO-UTOLA trial (NCT03745950), evaluating olaparib/placebo as maintenance after first-line platinum-based chemotherapy. Plasma samples were collected at screening after chemotherapy (baseline), 3 months (M3), and progression. ctDNA detection was assessed by a validated methylation-based digital-droplet PCR (MethddPCR) assay targeting DNA positions universally methylated in EC. Results: Among 130 evaluable patients, ctDNA was detected in 25/129 (19%, 1 technical fail) at baseline, 15/80 (19%) at M3, and 33/52 (63%) at progression. Baseline ctDNA positivity was independently associated with poorer progression-free survival (median 1.81 vs 7.39 months; adjusted-HR=5.33 3.17-8.97) and overall survival (OS) (10.3 vs 24.7 months; adjusted-HR=3.98 2.28-6.91) (adjusted for age, stage IV at diagnosis, p53abn subgroup, and residual measurable lesions after chemotherapy). Patients with baseline ctDNA had median OS of 9.36 months under olaparib versus 19.6 months under placebo (log-rank p=0.05). Patients with rising ctDNA at M3 had median PFS of 1.67 months, versus 9.64 months without, and median OS of 18.8 versus 25.8 months. ctDNA rising was predictive of poor post-progression OS under olaparib but not under placebo (interaction test, p0.001). Conclusion. MethddPCR-ctDNA is an independent prognostic biomarker for OS in advanced/metastatic EC. MethddPCR-ctDNA may identify patients unlikely to benefit from PARP inhibition, guide therapeutic decisions, and should be further evaluated as a new stratification parameter in future endometrial carcinoma trials.
Beinse et al. (Thu,) studied this question.
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