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2019 ASCO-SITC: Can Plasma Cell–Free DNA Aid in Predicting Response to Checkpoint Inhibitors in NSCLC?

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Key Points

  • The detection of a targetable oncogenic driver was associated with progressive disease on the first computed tomography.
  • The presence of a PTEN and/or STK11 mutations was correlated with poor outcomes, while the presence of transversion mutations in KRAS and/or TP53 predicted good outcomes.
  • Using cut-off of 30% and 50% of plasma response increased the ability of circulating tumor DNA to predict response.

Researchers hypothesized that targeting some genetic alterations in plasma cell–free DNA—along with early monitoring—could be an effective, noninvasive method for predicting response to immune checkpoint inhibitors in advanced non–small cell lung cancer (NSCLC). Findings from the IMMUNO-PREDICT trial were presented by Guibert et al at the 2019 ASCO-SITC Clinical Immuno-Oncology Symposium (Abstract 103).

Study Methods

Plasma samples were collected from 39 responders (with a progression-free survival longer than 6 months) and nonresponders (who had progressive disease at first evaluation) before nivolumab initation. Ninety-eight patients were tested at 1 month using tagged amplicon sequencing of hotspots and coding regions from 36 genes. The molecular profile of circulating tumor DNA and its early kinetics were analyzed as potential early indicators of response.

Genetic alterations in circulating tumor DNA were found in 78% of collected samples.

Findings

The detection of a targetable oncogenic driver was associated with progressive disease on the first computed tomography. The presence of a PTEN and/or STK11 mutations was correlated with poor outcomes, while the presence of transversion mutations in KRAS and/or TP53 predicted good outcomes. Combining these results, patients with a low “immune score” derived poor outcomes compared with patients with a high immune score. Studying early changes in 65 specimens, molecular response was correlated with clinical outcomes (progression-free survival = 14 months in patients with early ctDNA decrease vs 2 months in patients with increase, P < .0001; hazard ratio [HR] = 2.7). Using cut-off of 30% and 50% of plasma response increased the ability of circulating tumor DNA to predict response (HR = 4 and 4.17, respectively).

The authors concluded, “Targeted sequencing of plasma circulating tumor DNA and its early variations can predict response to anti–programmed cell death protein 1 [therapy].”

Disclosures: The study authors' full disclosures can be found at meetinglibrary.asco.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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