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<p>Circulating tumor DNA (ctDNA) ‘tumor fraction’ (TF) may correlate with therapy response, but little is known regarding TF dynamics immediately after therapy initiation. Plasma samples from a single-arm clinical trial enrolling patients with triple-negative breast cancer were collected at a variety of time points following infusion of onalespib (day -7), paclitaxel (day 1), and onalespib + paclitaxel (day 8). 313 samples from 14 patients underwent shallow whole genome sequencing and TF determination. The primary objective was to evaluate TF change from pre-infusion to 6 h and 24 h post-infusion. There was significant TF decline from pre-infusion to 6 h for paclitaxel (p = 0.03) but no change for onalespib or onalespib+paclitaxel at 6hl. There was no ctDNA TF surge within minutes to 24 h of onalespib, paclitaxel, or combination, despite an overall decline in TF during the first therapy cycle. However, there was significant decline in TF from pre-infusion to D9 (16% to 6.5%, p = 0.004). These findings support further research on ctDNA dynamics immediately after therapy initiation.</p>

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Acute circulating tumor DNA dynamics during and after systemic therapy initiation for advanced triple-negative breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月16日

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  • Briana To,
  • Vishnu Prasath,
  • Deloris Veney,
  • Christian Rolfo,
  • Viktor Adalsteinsson,
  • William E. Carson III,
  • Robert Wesolowski,
  • Daniel Stover,
  • Dionisia Quiroga

摘要

Circulating tumor DNA (ctDNA) ‘tumor fraction’ (TF) may correlate with therapy response, but little is known regarding TF dynamics immediately after therapy initiation. Plasma samples from a single-arm clinical trial enrolling patients with triple-negative breast cancer were collected at a variety of time points following infusion of onalespib (day -7), paclitaxel (day 1), and onalespib + paclitaxel (day 8). 313 samples from 14 patients underwent shallow whole genome sequencing and TF determination. The primary objective was to evaluate TF change from pre-infusion to 6 h and 24 h post-infusion. There was significant TF decline from pre-infusion to 6 h for paclitaxel (p = 0.03) but no change for onalespib or onalespib+paclitaxel at 6hl. There was no ctDNA TF surge within minutes to 24 h of onalespib, paclitaxel, or combination, despite an overall decline in TF during the first therapy cycle. However, there was significant decline in TF from pre-infusion to D9 (16% to 6.5%, p = 0.004). These findings support further research on ctDNA dynamics immediately after therapy initiation.