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WCLC 2022 | Improving target identification in patients with advanced NSCLC via up-front ctDNA

Wanda Cui, MBBS, BMedSci, FRACP, Peter MacCallum Cancer Centre, Melbourne, Australia, talks on an investigation into improving target identification in first-line advanced non-small cell cancer (NSCLC) via up-front circulating tumor DNA (ctDNA). Patients with newly diagnosed metastatic NSCLC were sequenced with ctDNA as well as with traditional tissue biomarker sequencing. The combination of ctDNA and tissue sequencing was able to detect 31% more tier 1 actionable variants than tissue sequencing alone. Additionally, the time to retrieving results was faster using ctDNA and the time to treatment was halved when using ctDNA to detect actionable variants. With tissue sequencing there are a number of challenges, such as retrieving enough tissue for adequate sequencing, which can be overcome with the use of ctDNA. With the number of targeted therapies increasing, the need for comprehensive next-generation sequencing (NGS) is urgent and using a combined approach may be able to decrease the rates of false-negatives when testing for biomarkers. This interview took place at the IASLC 2022 World Conference on Lung Cancer congress in Vienna, Austria.

Transcript (edited for clarity)

At the Marsden, our single institution, academic cancer center, we sequenced consecutive patients with newly diagnosed metastatic non-small cell lung cancer with circulating tumor DNA, using the Guardant360® platform, as well as using traditional biomarker sequencing on tissue. And what we were looking for is whether or not we were able to identify more actionable variants, with using the combination of ctDNA and tissue sequencing, which we detected...

At the Marsden, our single institution, academic cancer center, we sequenced consecutive patients with newly diagnosed metastatic non-small cell lung cancer with circulating tumor DNA, using the Guardant360® platform, as well as using traditional biomarker sequencing on tissue. And what we were looking for is whether or not we were able to identify more actionable variants, with using the combination of ctDNA and tissue sequencing, which we detected. So we detected I think about 30% extra tier one actionable variants, by using this approach, rather than using tissue alone. The other really important finding from this study was that we found that the time to getting biomarker results was faster using ctDNA and the time to treatment was half in patients that we were able to use ctDNA, to detect at an actionable variant.

And certainly we know that with tissue sequencing, there are a number of issues and challenges, certainly with sequential tissue sequencing that can take time, but also you need tissue, and in lung cancer patients it can be difficult to have adequate tissue for complete molecular sequencing. The other difficult is the heterogeneity of lung cancer and the fact that you can get false negatives. And one of the issues with that is now with improving targeted therapies, especially, rare mutations that we can now target. The need for NGS and comprehensive NGS is urgent, and certainly using a combined approach may be able to lower the rates of false negatives. One other strategy that we propose, obviously using a combined approach can be financially expensive, is whether or not we start with a ctDNA approach and then think about tissue molecular sequencing in patients, where we don’t find a targetable variant is another potential approach to think about. And certainly, I know there’s been recent ESMO, as well as IASLC guidelines, regarding using liquid biopsies to try and improve our detection of targetable, oncogenic driven lung cancers.

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