Plasma ctDNA as a treatment response biomarker in metastatic cancers: evaluation by the RECIST working group.
Alexander W WyattSaskia LitièreFrancois-Clement BidardLuc CabelLars DyrskjøtChris A KarlovichKlaus PantelJoan PetrieReena PhilipHillary S AndrewsPaz J VellankiSofie H TolmeijerXenia Villalobos AlberuChristian AlfanoJan BogaertsEmiliano CalvoHelen X ChenRodrigo De Almeida ToledoElisabeth G E de VriesLesley SeymourScott A LaurieElena GarraldaPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2024)
Early indicators of metastatic cancer response to therapy are important for evaluating new drugs and stopping ineffective treatment. The Response Evaluation Criteria in Solid Tumors (RECIST) based on repeat cancer imaging are widely adopted in clinical trials, are used to identify active regimens that may change practice, and contribute to regulatory approvals. However, these criteria do not provide insight before 6 - 12 weeks of treatment and typically require that patients have measurable disease. Recent data suggests that measuring on-treatment changes in the amount or proportion of circulating tumor DNA (ctDNA) in peripheral blood plasma may accurately identify responding and non-responding cancers at earlier time points. Over the past year, the RECIST working group has evaluated current evidence for plasma ctDNA kinetics as a treatment response biomarker in metastatic cancers and early endpoint in clinical trials, to identify areas of focus for future research and validation. Here, we outline the requirement for large standardized trial datasets, greater scrutiny of optimal ctDNA collection time points and assay thresholds, and consideration of regulatory body guidelines and patient opinions. In particular, clinically-meaningful changes in plasma ctDNA abundance are likely to differ by cancer type and therapy class, and must be assessed before ctDNA can be considered as a potential pan-cancer response evaluation biomarker. Despite the need for additional data, minimally-invasive on-treatment ctDNA measurements hold promise to build upon existing response assessments such as RECIST, and offer opportunities for developing novel early endpoints for modern clinical trials.
Keyphrases
- circulating tumor
- clinical trial
- papillary thyroid
- cell free
- circulating tumor cells
- small cell lung cancer
- minimally invasive
- squamous cell carcinoma
- peripheral blood
- squamous cell
- stem cells
- primary care
- combination therapy
- electronic health record
- machine learning
- end stage renal disease
- chronic kidney disease
- phase ii
- open label
- replacement therapy
- ejection fraction
- mass spectrometry
- photodynamic therapy
- phase iii
- robot assisted
- single molecule
- peritoneal dialysis
- drug induced
- quality improvement
- nucleic acid
- lymph node metastasis
- fluorescence imaging