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ctDNA is prognostic of worse outcomes for CDK4/6 therapy

Presented by
Prof. Sherene Loi, Peter MacCallum Cancer Centre, Australia
Conference
ASCO 2024
Trial
Phase 3, monarchE
Doi
https://doi.org/10.55788/c7c2526b
The presence of circulating tumour DNA (ctDNA) is a highly prognostic indicator of worse treatment outcomes, particularly for patients who were persistently ctDNA-positive, as demonstrated in the monarchE trial.

Patients with node-positive early breast cancer are at high risk of recurrence (up to 30% at 5 years) [1]. The monarchE trial (NCT03155997) showed a sustained benefit of 2 years of adjuvant abemaciclib to endocrine therapy in patients with HR-positive/HER2-negative, node-positive, high-risk early breast cancer: 7.6% and 6.7% absolute improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS), respectively [2].

To evaluate the prognostic value of ctDNA detection and its dynamics, Prof. Sherene Loi (Peter MacCallum Cancer Centre, Australia) and colleagues analysed a representative subset of participants from the monarchE trial [3].

Of the 5,637 participants enrolled in monarchE, ctDNA was obtained from 910 participants at baseline; ≥1 post-baseline sample was obtained from 889 participants. A consistent treatment effect was observed in the total population and the subpopulation with ctDNA samples (IDFS HR 0.68 and 0.67, respectively).

The ctDNA detection rate at baseline was 8% (n=70). Among participants who were ctDNA-negative at baseline (n=840), 10% became positive on treatment. Among participants who were ctDNA-positive at baseline (n=92), 59% remained positive on treatment.

Baseline ctDNA detection proved to be associated with worse invasive disease-free survival (IDFS) outcomes: the 4-year IDFS rate was 79.1% in baseline ctDNA-negative participants versus 20.0% in baseline ctDNA-positive participants (P<0.0001). Participants who remained ctDNA-positive or became ctDNA-positive on treatment were more likely to experience an IDFS event than those who became ctDNA-negative or remained ctDNA-negative (see Figure).

Figure: ctDNA status associated with treatment outcomes in monarchE [3]



In addition, more distant recurrence was observed in participants who were ctDNA-positive at baseline than in those who were ctDNA-negative.

Based on these outcomes, Prof. Loi concluded that “ctDNA detection was highly prognostic of worse treatment outcomes, particularly in patients who were persistently ctDNA-positive. Further intensification of treatment with novel therapeutics should be considered for these patients.”

  1. Sheffield KM et al. Future Oncol. 2022;18:2667-2682.
  2. Rastogi P, et al. J Clin Oncol. 2024;42:987-993.
  3. Loi S, et al. Prognostic utility of ctDNA detection in the monarchE trial of adjuvant abemaciclib plus endocrine therapy (ET) in HR+, HER2-, node-positive, high-risk early breast cancer (EBC). Abstract LBA507, ASCO Annual Meeting 2024, 31 May–4 June, Chicago, IL, USA.

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