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Purpose <p>To characterize long-term (LT) and short-term (ST) responders to the Poly (ADP-ribose) polymerase inhibitor olaparib in the primary and recurrent maintenance setting.</p> Methods <p>Clinical and molecular data was collected for patients receiving maintenance olaparib between January 2014 and July 2021. ST responders were defined as those experiencing progression &lt; 6&#xa0;months from initiating olaparib, whereas LT responders exhibited response ≥ 2&#xa0;years. Molecular analysis included germline <i>BRCA1/2</i> status, Myriad MyChoice CDx Homologous Recombination Deficiency (HRD) somatic testing, and STRATA Select comprehensive genomic profiling.</p> Results <p>124 patients who received olaparib were included; 45 (36.3%) LT and 31 (25.0%) ST responders were identified. <i>BRCA2</i> mutations were enriched among the LT responders compared to ST responders (16 (35.5%) v. 4 (12.9%), <i>p</i> = 0.028) and LT responders were more likely to be HRD (40 (88.9%) v 19 (61.3%), <i>p</i> = 0.005). Patients receiving olaparib following platinum-sensitive recurrence were more likely to experience ST response compared to the primary setting (24 (55.8%) vs 7 (21.2%), <i>p</i> = 0.002). In both the primary and recurrent setting, LT responders were more likely to have a complete response to the most recent chemotherapy when compared to those experiencing ST response (24 (92.3%) v. 3 (42.9%), for primary maintenance, <i>p</i> = 0.021 and 10 (52.6%) v. 3 (12.5%) for recurrent, <i>p</i> = 0.004).</p> Conclusions <p>LT response to olaparib for primary maintenance is common, and more frequently observed in patients with a complete response to platinum-based chemotherapy. <i>BRCA2</i> mutations conferred exceptional benefit to olaparib. Durable benefit was more commonly observed in patient’s receiving frontline maintenance olaparib.</p>

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Clinical and molecular determinants of response to maintenance olaparib for primary and recurrent epithelial ovarian carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月20日

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  • Matthew K. Wagar,
  • Kharmen Bharucha,
  • Lauren Montemorano,
  • Laura B. Huffman,
  • Amy L. Godecker,
  • Lisa M. Barroilhet

摘要

Purpose

To characterize long-term (LT) and short-term (ST) responders to the Poly (ADP-ribose) polymerase inhibitor olaparib in the primary and recurrent maintenance setting.

Methods

Clinical and molecular data was collected for patients receiving maintenance olaparib between January 2014 and July 2021. ST responders were defined as those experiencing progression < 6 months from initiating olaparib, whereas LT responders exhibited response ≥ 2 years. Molecular analysis included germline BRCA1/2 status, Myriad MyChoice CDx Homologous Recombination Deficiency (HRD) somatic testing, and STRATA Select comprehensive genomic profiling.

Results

124 patients who received olaparib were included; 45 (36.3%) LT and 31 (25.0%) ST responders were identified. BRCA2 mutations were enriched among the LT responders compared to ST responders (16 (35.5%) v. 4 (12.9%), p = 0.028) and LT responders were more likely to be HRD (40 (88.9%) v 19 (61.3%), p = 0.005). Patients receiving olaparib following platinum-sensitive recurrence were more likely to experience ST response compared to the primary setting (24 (55.8%) vs 7 (21.2%), p = 0.002). In both the primary and recurrent setting, LT responders were more likely to have a complete response to the most recent chemotherapy when compared to those experiencing ST response (24 (92.3%) v. 3 (42.9%), for primary maintenance, p = 0.021 and 10 (52.6%) v. 3 (12.5%) for recurrent, p = 0.004).

Conclusions

LT response to olaparib for primary maintenance is common, and more frequently observed in patients with a complete response to platinum-based chemotherapy. BRCA2 mutations conferred exceptional benefit to olaparib. Durable benefit was more commonly observed in patient’s receiving frontline maintenance olaparib.