Detection of residual disease and recurrence in early-stage non-small cell lung cancer (NSCLC) patients using sensitive personalized ctDNA sequencing assays.

Authors

null

Katrin Heider

Cancer Research UK Cambridge Institute, Cambridge, United Kingdom

Katrin Heider , Davina Gillian Gale , Giovanni Marsico , Andrea Ruiz-Valdepeñas , Garima Sharma , Malcolm Perry , Robert Osborne , Karen Howarth , Viona Rundell , Jelena Belic , Jerome Wulff , Susan Harden , Doris M Rassl , Robert Rintoul , Nitzan Rosenfeld

Organizations

Cancer Research UK Cambridge Institute, Cambridge, United Kingdom, Inivata Ltd, Cambridge, United Kingdom, Cambridge Clinical Trials Unit-Cancer Theme, Cambridge, United Kingdom, Addenbrookes Hospital, Cambridge, United Kingdom, Royal Papworth Hospital NHS Foundation Trust, Cambridge, United Kingdom, Department of Oncology, University of Cambridge, Cambridge, United Kingdom

Research Funding

Pharmaceutical/Biotech Company
Inivata, Cancer Research UK

Background: Detection of residual circulating tumour DNA (ctDNA) in patient plasma following curative intervention for localized non-small cell lung cancer (NSCLC) could identify patients who are at higher risk of relapse. These patients may benefit from adjuvant treatment, even if they have no macroscopic disease identified by radiographic imaging, which is the current standard of care. Here we evaluate the performance of the Inivata personalized sequencing assays to detect ctDNA in a cohort of 90 patients with early-stage NSCLC undergoing treatment with curative intent. Methods: The Inivata assay uses a highly sensitive next-generation sequencing platform, to identify tumor-specific variants from exome sequencing of tumor tissue and to track up to 48 patient-specific mutations in plasma specimens by multiplex PCR and ultra-high-depth next-generation sequencing. Samples from 90 patients with Stage I-III NSCLC who underwent radical treatment with curative intent, either surgery or radiotherapy ± chemotherapy, were collected as part of the LUng cancer - CIrculating tumor DNA (LUCID) study. Results: 350 plasma samples from 90 patients were analyzed using the Inivata assay, including samples collected before and after treatment and at subsequent follow-up visits. ctDNA was detected in pre-treatment samples in 38% of 32 patients (12/32) with Stage I NSCLC and in 90% of 21 patients (19/21) with Stage II/III disease, at allele fractions ranging from 6 parts per million (ppm, equivalent to 0.0006%) to over 20,000 ppm (equivalent to 2%). In plasma samples collected post-treatment, ctDNA was detected in close to 50% of cases. Conclusions: These findings highlight the Inivata assay is a sensitive method for detection of residual ctDNA and recurrence in early stage NSCLC. Initial detection rates ranged from 38% in Stage I disease to 90% for patients with Stage II/III disease prior to treatment, including detection of ctDNA to levels as low as a few parts per million. ctDNA was detected in at least one post-treatment timepoint in close to 50% patients. Together with additional data to be presented from the full 90 patient cohort, this suggests a possible route to improving treatment and designs of adjuvant trials for early stage NSCLC by detection of residual disease post-treatment and monitoring for early detection of relapse.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Publication Only

Session Title

Publication Only: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Track

Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Sub Track

Circulating Biomarkers

Citation

J Clin Oncol 38: 2020 (suppl; abstr e15560)

DOI

10.1200/JCO.2020.38.15_suppl.e15560

Abstract #

e15560

Abstract Disclosures

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