AACR Annual Meeting 2021 – An overview
Greg Jones our Sr Director, Medical Affairs provides an overview of the growing evidence for ctDNA changing how we detect residual disease and recurrence.
The American Association for Cancer Research (AACR) meeting is one of the world’s largest cancer-focused conferences. It covers a large spectrum of cancer research ranging from cancer biology, translational research, pre-clinical and clinical studies to survivorship and advocacy.Due to the COVID-19 pandemic, the 2021 AACR annual meeting was held entirely virtually, with week 1 taking place from 10-15 April, whilst Week 2 will take place from 17-21 May.
Latest advance and broader adoption of liquid biopsy in precision oncology
In recent years, researchers have investigated the use of liquid biopsy across the treatment paradigm from advanced disease to early detection/screening and monitoring of recurrence. The AACR 2021 meeting showcased some of the latest developments in this rapidly growing field.
Beyond guiding targeted treatment selection, the new frontier in the clinical applications of liquid biopsy is in the use of liquid biopsy-based testing throughout all stages of cancer. For example, it can be used in cancer screening, as a prognostic biomarker, for monitoring of treatment response and as a sensitive tool for recurrence detection in early-stage cancer patients, the latter of which is of growing interest. In fact, there is increasing evidence which shows the potential for the use of circulating tumor DNA (ctDNA) in the detection of minimal residual disease (MRD) and for following patients over time to identify early signs of tumor relapse.
This topic was highlighted in the on-demand session “ADT11.OD – Noninvasive Monitoring of Minimal Residual Disease with Liquid Biopsies Towards Real-Time Treatment Decision Making”. Three presentations from international experts discussed ongoing prospective clinical trials in colorectal cancer, breast cancer, non-small cell lung cancer (NSCLC) and the potential integration of plasma-based cell free DNA (cfDNA) methylation signatures and cfDNA genome-wide sequencing into MRD analysis.
In the e-poster session and live presentations, ongoing research into the uses of liquid biopsy in different clinical settings were largely explored. Topics included detection of early-stage cancer and minimal residual disease, monitoring of advanced disease and molecular resistance, bioinformatic analysis of ctDNA sequencing and the use of circulating RNA, protein biomarkers, and methylation analysis to enhance assay performance.
Patrick Forde of Johns Hopkins University presented a subgroup analysis of the use of ctDNA in the CheckMate-816 Phase 3 trial exploring the neoadjuvant use of nivolumab + chemo vs chemo only in resectable NSCLC patients. Here they showed that ctDNA clearance was associated with pathological complete response (pCR) allowing researchers a potential tool to assess the impact of neoadjuvant therapy during the course of the therapy.
Inivata’ Residual Disease and Recurrence (RaDaR) posters: Updates from the virtual AACR 2021 meeting
Inivata highlighted new data at the AACR meeting on our RaDaR® assay in support of the capabilities and application for the detection of MRD and cancer recurrence. In two studies, RaDaR demonstrated remarkable specificity (100%) and sensitivity (100%) in detecting clinical progression in patient cohorts with early-stage breast cancer and head and neck cancer.
In the early-stage breast cancer study, personalized RaDaR assays were carried out on samples from 22 patients who had undergone surgery with curative intent, from whom 147 plasma samples were analyzed for ctDNA across multiple timepoints. MRD was identified by RaDaR in 100% of the relapsed patients (17/17) and in none of the patients that did not relapse. This included patients with brain only metastasis, which was not previously achievable with single mutation digital PCR MRD-detection assays. Detection of ctDNA levels ranged from 0.0007% variant allele fraction (VAF) to 1.3% VAF. Median lead-time from ctDNA detection to clinical relapse (in patients where relapse occurred outside of the brain) was 12.89 months, with a maximum lead-time of over two years. In patients with inter-cranial disease relapse only, the average lead time was 4.5 months. The study was run in collaboration between Inivata, The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust.
RaDaR is also being used in the LIONESS study (Liquid BIOpsy for MiNimal RESidual DiSease Detection) in head and neck squamous cell carcinoma (HNSCC). In this ongoing single-center prospective experimental evidence-generating study, patients who had received surgery with curative intent are monitored for MRD and recurrence using RaDaR. Preliminary data from the 11 stage III/IV patients recruited to-date shows 100% ctDNA detection in baseline samples taken prior to surgery. In all patients (4/4) who have gone on to relapse, ctDNA was detected ahead of clinical progression, with a lead time of 108-248 days. In these post-surgery samples, ctDNA could be detected at levels as low as 0.0006% VAF. The study is being conducted in collaboration with the Department of Otorhinolaryngology, Head and Neck Surgery (ORL-HNS), LMU Klinikum, and Institute of Pathology, Faculty of Medicine, LMU Munich.
These data highlight the value of RaDaR’s exceptional assay performance and its capabilities across different solid tumor types building on the evidence previously reported in NSCLC, where RaDaR detected ctDNA 6-12 months ahead of clinical progression in the majority of cases, as well as predicting lower progression free survival (PFS). We are delighted about these results and are excited to see what more is to come from the studies that are currently underway.
In case you missed us at this year’s AACR, the RaDaR posters presented and other scientific resources including an InVisionFirst Lung poster, previous posters, papers and blogs can be found on our website. You can also find out about how RaDaR™ has recently received Breakthrough Device Designation from the FDA. If you wish to know more about how highly sensitive and specific ctDNA detection and accurate monitoring may enhance your studies and clinical trials, please contact us for more information.
Forde PM, Spicer J, Lu S, et al. Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo as neoadjuvant treatment (tx) for resectable (IB-IIIA) non-small cell lung cancer (NSCLC) in the phase 3 CheckMate 816 trial. Presented at: AACR Annual Meeting; April 10-15, 2021; virtual. Abstract CT003.
Cutts RJ, Coakley M, Garcia-Murillas I, Ulrich L, Howarth K, Emmett W, Perry M, Ellis P, Knape C, Johnston SRD, Ring A, Russell S, Evans A, Skene A, Wheatley D, Dowsett M, Smith I E, Turner NC. Molecular residual disease detection in early-stage breast cancer with a personalized sequencing approach. Presented at: AACR Annual Meeting; April 10-15, 2021; virtual. Abstract 536.
Flach S, Howarth K, Hackinger S, Pipinikas C, McLay K, Marsico G, Walz C, Gires O, Canis M, Baumeister P. Personalized circulating tumor DNA analysis in head and neck squamous cell carcinoma: Preliminary results of the Liquid BIOpsy for MiNimal RESidual DiSease Detection in Head and Neck Squamous Cell Carcinoma (LIONESS) study. Presented at: AACR Annual Meeting; April 10-15, 2021; virtual. Abstract 553.