2022 ASCO® Annual Meeting: Highlights and observations

Liquid biopsy highlights

Inivata had five data releases at the meeting, the highest profile of which was a podium presentation for the “Circulating tumor DNA (ctDNA) and late recurrence in high-risk, hormone receptor–positive, HER2-negative breast cancer (CHiRP) Study”, a collaboration with researchers at the Dana-Faber Cancer Institute, presented at the “ctDNA, dawn of a New Era” session. The project was also highlighted (alongside the LIONESS study) in the daily ASCO news. The presentation was accompanied by co-publication of this study in the Journal of Clinical Oncology1. The data, presented by Dr Marla Lipsyc-Sharf, aimed to investigate circulating tumor DNA (ctDNA) detection and its association with metastatic recurrence in high-risk, early-stage hormone receptor-positive breast cancer (HR+ BC), in patients more than five years from diagnosis, when over half of metastatic relapses are known to occur. This is, to our knowledge, the first data release investigating plasma ctDNA analysis for MRD detection in this large patient group. Ten percent of patients were found to be MRD positive more than five years from diagnosis, despite no clinical evidence of metastatic recurrence at the time of first plasma sample. The RaDaR assay identified ctDNA in advance of all cases of distant metastasis with significant lead times (median of over a year and up to 38.5 months in advance), and its detection was associated with a shorter relapse-free survival. It is hoped that this work may help inform future prospective studies of liquid biopsy to prevent or delay later recurrence of early-stage breast cancer.

The same session also saw an exciting data release from the DYNAMIC study, led by Jeanne Tie, MD, sharing novel, persuasive clinical utility data supporting the use of MRD monitoring in stage II colorectal cancer after surgery to determine those who will benefit from adjuvant chemotherapy. While there is currently a large body of evidence supporting the prognostic value of MRD testing in detecting cancer recurrence at an early stage, up to now clinical utility in a prospective, randomized setting had not yet been demonstrated. The DYNAMIC study reported non-inferiority of ctDNA-guided treatment vs standard management in terms of 2-year recurrence-free survival, yet with the use of adjuvant chemotherapy being almost halved in the ctDNA guided arm. This data demonstrates the potential for safe, de-escalation in ctDNA-negative patients, with clinically low risk, stage II disease. Conversely, the rate of recurrence among those who received chemotherapy was low for patients with ctDNA detected after surgery, suggesting a survival benefit from adjuvant chemotherapy. The study was also published concurrently in the New England Journal of Medicine2. A major step forward for the field, this is likely to be the first of many upcoming studies prospectively investigating the clinical utility of ctDNA detection for MRD monitoring in various cancer subtypes and clinical scenarios which will likely emerge over the next few years.

Regarding the further Inivata data releases, four poster presentations demonstrating the use of the RaDaR assay in Head and Neck Squamous Cell Carcinoma (two posters), Melanoma, and a real-world data study highlighting how InVisionFirstTM Lung can accelerate time to treatment for advanced NSCLC patients, also provoked long and varied discussions at their respective poster sessions. The LIONESS study in Head and Neck Squamous Carcinoma was also selected to be presented at a well-attended poster discussion session, and similar to the CHIRP study, was reported on in the ASCO daily news. This study is an ongoing, prospective study in collaboration with the University of Munich- for more information on the study, read: Liquid biopsy highlights from the ESMO 2021 virtual congress.

References

1. Circulating Tumor DNA and Late Recurrence in High-Risk Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer. Marla Lipsyc-Sharf et al. Journal of Clinical Oncology, 2022.
2. Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer. Jeanne Tie et al. New England Journal of Medicine, 2022.

PDF versions of the ASCO posters can be found here:

• Circulating Tumor DNA and Late Recurrence in High-Risk Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer
• Plasma First – Accelerating Lung Cancer Diagnosis through Liquid Biopsy
• Liquid bIOpsy for miNimal rESidual diSease detection in Head and Neck Squamous Cell Carcinoma (LIONESS) – A personalized cell-free tumor DNA analysis for patients with HNSCC
• Leveraging personalized circulating tumor DNA (ctDNA) for detection and monitoring of molecular residual disease in high-risk melanoma
• Personalized circulating tumor DNA (ctDNA) analysis in patients with recurrent/metastatic Head & Neck Squamous Cell Cancer (R/M HNSCC)