ASCO Conference Coverage

Durvalumab and Olaparib Enhance ctDNA Clearance in First-Line Treatment of Endometrial Cancer

Miranda Manier, BA

Key Highlights

  • Baseline circulating tumor DNA detection was associated with shorter progression-free survival across treatment arms.
  • Addition of durvalumab to carboplatin/paclitaxel resulted in more rapid reductions in circulating tumor DNA levels compared to chemotherapy alone.
  • Maintenance olaparib further decreased circulating tumor DNA levels and improved clearance rates, particularly in mismatch repair proficient patients.
  • The combination of durvalumab, chemotherapy, and maintenance olaparib showed limited additional impact on circulating tumor DNA in mismatch repair deficient tumors.

In a post hoc exploratory analysis of the phase 3 DUO-E trial, researchers investigated changes in circulating tumor DNA (ctDNA) during first-line treatment of newly diagnosed endometrial cancer. The results, which were presented at the 2025 American Society of Clinical Oncology Annual Meeting, showed that the presence of ctDNA at baseline was associated with shorter progression-free survival across all treatment arms. The addition of durvalumab to carboplatin/paclitaxel chemotherapy was linked to more substantial reductions in ctDNA detection compared with chemotherapy alone, and maintenance olaparib further decreased ctDNA levels in mismatch repair proficient tumors.

The DUO-E trial had previously demonstrated that adding durvalumab to chemotherapy improved progression-free survival in the overall patient population, with exploratory analyses suggesting an added benefit of maintenance olaparib in mismatch repair proficient tumors. However, the impact of these treatments on ctDNA, a potential biomarker of treatment response, had not been characterized in detail. This analysis aimed to fill that gap by exploring how ctDNA changed over time in relation to treatment regimens.

Eligible patients were randomized 1:1:1 to receive either chemotherapy alone, chemotherapy plus durvalumab followed by durvalumab maintenance, or chemotherapy plus durvalumab followed by maintenance with durvalumab and olaparib. The researchers analyzed ctDNA in plasma samples collected at baseline (cycle 1, day 1), during chemotherapy (cycle 3, day 1), prior to maintenance (cycle 7, day 1), and during maintenance (cycle 9, day 1) using the Guardant Infinity methylation-based assay. The biomarker-evaluable population included 347, 349, 350, and 349 patients at these respective time points.

At baseline, ctDNA was detected in 80% of patients, and its presence was associated with shorter progression-free survival across all treatment arms. During chemotherapy, the addition of durvalumab led to greater reductions in ctDNA detection by cycle 3, day 1 (26% with durvalumab vs 44% with chemotherapy alone). This effect persisted into maintenance, with detection rates at cycle 9, day 1 of 33% for durvalumab versus 50% for chemotherapy alone. In mismatch repair proficient tumors, maintenance olaparib further reduced ctDNA detection at cycle 9, day 1 (26% for durvalumab plus olaparib vs 36% for durvalumab alone), with a higher proportion of patients achieving ctDNA clearance between cycle 7 and cycle 9 (48% vs 17%). In mismatch repair deficient tumors, maintenance olaparib had minimal impact on ctDNA dynamics. These findings suggest that the addition of durvalumab and maintenance olaparib enhances ctDNA clearance, particularly in mismatch repair proficient tumors.

“In this post hoc exploratory analysis, baseline circulating tumor DNA was associated with shorter progression-free survival,” the authors concluded. “The addition of durvalumab was associated with rapid reductions in ctDNA detection during chemotherapy and less re-emergence of ctDNA during maintenance. The addition of maintenance olaparib was associated with further reduction of detectable ctDNA and increased ctDNA clearance in mismatch repair proficient patients, reflecting an additional activity of the combination.”

Reference

Westin SN, Moore KN, Guy M, et al. Durvalumab plus carboplatin/paclitaxel followed by durvalumab with or without olaparib as first-line treatment for endometrial cancer: Longitudinal changes in circulating tumor DNA. Presented at: 2025 American Society of Clinical Oncology (ASCO) Annual Meeting; 2025 May 30–June 3; Chicago, IL.