The Friends of Cancer Research (Friends) held a meeting in Washington, DC, to update attendees on data regarding circulating tumor DNA (ctDNA), a novel biomarker now under intensive study. This emerging biomarker-genetic material shed from cancer cells and found in the bloodstream-holds the promise of identifying cancer patients who respond to treatment by evaluating the presence and levels of ctDNA in a blood sample (liquid biopsy).
If its potential in oncology is realized, meeting speakers said ctDNA could not only simplify the monitoring of treatment response, but also accelerate drug development and make it easier for patients to participate in clinical trials. This could lead to more diversity in patient enrollment and facilitate the subtyping of disease that could lead to earlier diagnosis and be useful in detecting minimal residual disease.
As previously reported by Oncology Times, Friends launched a multi-stakeholder research partnership to generate data on ctDNA and study whether changes in this biomarker are associated with long-term outcomes for cancer patients under treatment.
"We are trying very hard to get the evidence that we need," said Ellen Sigal, PhD, Friends Chair and founder. Noting that it will take "a lot of work to get the job done," Sigal said the research partnership has one goal and one goal only-to help patients. Friends has produced a roadmap designed to help facilitate the development of ctDNA as an early endpoint.
"We are at a stage where we need to collect more information," said keynote speaker Patrizia Cavazzoni, MD, Director of the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA). She said that, when it comes to identifying novel endpoints such as ctDNA, "Once again, the cancer community is at the leading edge. You're continuing to be the pathfinders." Cavazzoni noted that FDA released a draft guidance document in May 2022 for drug sponsors who plan to use plasma-derived ctDNA as a biomarker in cancer clinical trials under an investigational new drug application, and/or to support marketing approvals of drugs and biologicals that treat solid tumors in the early-stage setting.
Looking ahead, ctDNA technology development may benefit from a newly proposed Medicare coverage pathway to expedite breakthrough technologies-the Transitional Coverage for Emerging Technologies (TCET) pathway. Announced June 22, 2023, the proposed TCET pathway includes an evidence development framework that provides manufacturers with opportunities to engage with the Centers for Medicare & Medicaid Services (CMS) in pre-market communications, said keynote speaker Lee Fleisher, MD, Chief Medical Officer and Director of the Center for Clinical Standards and Quality at CMS.
At the meeting, Friends presented data from the ctDNA for Monitoring Treatment Response (ctMoniTR) Project and the Baseline ctDNA Project. The ctMoniTR project is designed to find out whether changes in ctDNA reflect response to treatment. The baseline ctDNA project will perform a descriptive meta-analysis to compare trends in baseline ctDNA before current treatment between cancer types and stages, with the hope of informing a conceptual framework for using ctDNA as an early endpoint that predicts long-term outcomes.
Data from the baseline ctDNA project covers 2,327 early-stage samples and 63,127 late-stage samples of non-small cell lung cancer (NSCLC), 11,235 late-stage prostate cancer samples, 10,532 late-stage breast cancer samples, 1,359 late-stage bladder cancer samples, and 956 late-stage head and neck squamous cell carcinoma samples. The data are disparate across ctDNA technologies, stressing the need for data harmonization and standardization-a key theme at the Friends meeting. There is variability in the frequency of ctDNA detection in NSCLC, with late-stage NSCLC having a higher proportion of detected ctDNA.
Panelist Anand Pathak, MD, PhD, MPH, Medical Officer at the FDA, noted there are many assays for ctDNA, tumor types may have different shedding of ctDNA, it is important to know the timing of the collection of ctDNA blood samples, and data standardization for clinical trials is needed to make the ctDNA data more poolable.
Data standards, data harmonization, and data sharing will be needed to move research on ctDNA forward, emphasized panelist James L. Chen, MD, Associate Professor in the Departments of Internal Medicine and Biomedical Informatics at Ohio State University. As a sarcoma oncologist, he noted it will be important to include rare cancers in research on ctDNA, because "the rare cancers are often overlooked."
Chen stressed that research on ctDNA needs to be collaborative. "Data sharing has to be public. This can't be a secret." He emphasized the value of consortia in moving research on ctDNA forward.
Data from Step 2 of ctMoniTR covers eight advanced cancers, 20 clinical trials, 3,000 patients, and 16 different therapies. Step 2 covers advanced NSCLC patients treated with tyrosine kinase inhibitors (anti-EGFR, ALK, MET, RET) in the first module. Step 1 of this project, which covered five clinical trials and 200 patients with advanced NSCLC treated with anti-PD-L1, has already shown "robust and consistent associations between changes in ctDNA and patient outcomes for patients with advanced NSCLC receiving immunotherapy," noted Friends.
Results from Step 2-which will be released throughout 2023 and 2024-have shown that harmonizing data across clinical trials was feasible and patients with detected ctDNA at baseline who had no detected ctDNA after treatment had improved outcomes. Thus, the data demonstrate that molecular response is associated with improved patient outcomes.
The data show that ctDNA as an early endpoint really does correlate with patient outcomes, added panelist Nicole Gormley, MD, Acting Associate Director for Oncology Endpoint Development at FDA's Oncology Center of Excellence. As such, she said, ctDNA has the potential to be a powerful biomarker with many uses. Gormley agreed with Chen that collaboration is needed, adding that now what is also needed is to study and learn how to use ctDNA as an endpoint in clinical trials. She said it is important to identify what threshold of ctDNA is clinically meaningful and what threshold correlates with long-term clinical benefit.
Ken Billett, a panelist, patient advocate, and Stage IV melanoma survivor, stressed the importance of education-professional and public-to inform people of the benefits of ctDNA. He said such education may help increase clinical trial participation, thus enhancing data collection.
Agreeing on the need for education on ctDNA was panelist Christian Rolfo, MD, PhD, MBA, Professor of Medicine (Hematology and Medical Oncology) at the Icahn School of Medicine at Mount Sinai and Associate Director for Clinical Research in the Center for Thoracic Oncology at the Tisch Cancer Institute. He said a team approach should be taken so nurse practitioners and other health care professionals are brought into the field of ctDNA as an emerging biomarker. Rolfo also stressed the need for a global approach to research on the new biomarker, noting patient needs may be different in different countries.
Peggy Eastman is a contributing writer.