Liquid biopsy highlights from the ESMO 2021 virtual congress
Dr Mike Nahorski, Director of Clinical and Scientific Alliances provides a perspective of ESMO2021.
The ESMO congress is the largest and most influential oncology meeting in Europe and attracts upward of 30,000 people from across the world to share new clinical data and scientific discoveries across cancer care, diagnostics and therapeutics. Originally scheduled to be in Paris, the ongoing COVID-19 travel restrictions once again resulted in the congress being run as a predominantly virtual affair, however a number of presenting authors were able to attend the meeting in person, allowing highly interactive debates and Q+A sessions (and to no doubt enjoy some wonderful Parisian hospitality). Alongside high-profile data presentations supporting new therapy regimes in HER2+ breast¹, colorectal² and cervical cancers³, a number of interesting advances in the field of liquid biopsy were also presented.
Liquid biopsy research has become a hot topic in recent years, with the potential for transforming patient treatment and monitoring across multiple cancer types and indications. With ctDNA testing already established as a tool for identifying tumor drivers and resistance mutations within a person’s circulation without the need for solid biopsy, further applications were also presented at ESMO. These extend across the cancer treatment spectrum, from using liquid biopsy to screen asymptomatic individuals in early cancer4, to personalized assays for detecting residual disease after curative-intent therapy5,6 and utilizing ctDNA kinetics to predict patient treatment outcomes in more advanced patients7.
An interesting debate on whether targeting molecular residual disease (MRD) in solid tumours will increase cure rates took place on the Friday evening. With the field of MRD detection by ctDNA testing being a relatively new one, data is only beginning to emerge to help address this question. However, results shared during the debate from the recent IMvigor010 study in operable urothelial cancer8, where treatment with adjuvant-based atezolizumab showed improved survival only in patients for whom ctDNA was positive at the start of therapy, provided a tantalizing glimpse into the potential for such technologies. Nonetheless 79% of the voting audience felt that currently the clinical utility for predictive use (treatment selection) has not yet been established. This will undoubtedly be an area of significant focus for the field over the next few years.
Evidence to support the utility of ctDNA testing in the early detection of MRD and cancer recurrence is already accumulating. At ESMO 2021, Inivata highlighted data to further support this approach using RaDaR™, its personalized and highly sensitive assay for MRD detection, in patient cohorts with head and neck squamous cell carcinoma and early-stage breast cancer.
The first study aimed to use RaDaR to assess ctDNA levels in a prospective cohort of patients with stage I-IV head and neck squamous cell carcinoma in collaboration with the University of Munich. 21 patients donated a total of 121 plasma samples pre- and post-operatively, before the start of adjuvant therapy and at follow up visits, which were then tested for the presence of ctDNA. Accurate detection of ctDNA in the blood at post operative timepoints can be very challenging due to the low levels of residual tumor DNA in the blood at this time. However, in all cases with clinical recurrence collected to date, ctDNA was detected prior to clinical progression with lead times ranging from 108 to 298 days, and detection of ctDNA at as low as six parts per million, or0.0006% variant allele frequency (VAF). The authors reported that this early detection of relapse using ctDNA could indicate patient populations where earlier therapeutic intervention may be beneficial5.
The second poster, a collaboration with the University Hospital in Ulm, evaluated the clinical utility of RaDaR in a retrospective analysis of early-stage breast cancer patients after standard treatment. RaDaR was able to detect the presence of ctDNA in plasma to levels as low as 0.0029% VAF. The results presented demonstrated that ctDNA detection is strongly associated with distant recurrence in this patient group, with 12 of 13 distant recurrence cases being successfully detected. The undetected recurrence specimen may be indicative of an alternative origin or second primary tumor rather than a recurrence6.
These results add to a growing body of evidence for the potential clinical utility of the RaDaR assay across various tumor types, with further examples having been recently shared at the springtime ASCO and AACR congresses, demonstrating the value of longitudinal ctDNA monitoring in early-stage NSCLC and early breast cancer. In addition, two further posters were presented at ESMO demonstrating the real-time clinical utility of the InVisionFirst®-Lung assay, which uses the same genetic testing platform as RaDaR for ctDNA detection, but is designed to stratify late-stage NSCLC patients based on the presence of driver and resistance mutations within ctDNA in the patient’s circulation.
Overall, this was a dynamic and exciting meeting with numerous advances presented across the breadth of clinical cancer research, which provided a highly interactive forum despite the limitations of a mostly virtual event. In case you missed any of our recent disclosures, they can be found on the Inivata website and do look out for our next data releases for RaDaR, which will hopefully be presented in person, at the San Antonio Breast Cancer symposium in December.
- LBA1 – Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (Pts) with HER2+ metastatic breast cancer (mBC): Results of the randomized phase III DESTINY-Breast03 study. Javier Cortes. ESMO 2021.
- KRYSTAL-1: Adagrasib (MRTX849) as Monotherapy or Combined with Cetuximab (Cetux) in Patients (Pts) With Colorectal Cancer (CRC) Harboring a KRASG12C Mutation. Jared Weiss. ESMO 2021.
- Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer: randomized, double-blind, phase 3 KEYNOTE-826 study. Nicoletta Colombo et al. ESMO 2021.
- Comprehensive Evaluation of Cell-Free DNA (cfDNA) Multi-Omics for Multi-Cancer Early Detection (MCED). Liu M.C et al. ESMO 2021.
- Personalised circulating cell-free tumour DNA analysis for detection of minimal residual disease and recurrence in patients with head and neck squamous cell carcinoma. Susanne Flach et al. ESMO 2021.
- A personalised sequencing approach for liquid biopsy-based detection of recurrent disease in early-stage breast cancer. Wolfgang Janni et al. ESMO 2021.
- Circulating tumor DNA kinetics in recurrent/metastatic head & neck squamous cell cancer (R/M HNSCC) patients. Kirsty Taylor et al. ESMO 2021.
- ctDNA guiding adjuvant immunotherapy in urothelial carcinoma. Powles T et al. Nature. 2021.