New research led by Friends of Cancer Research (Friends) shows that decreases in circulating tumor DNA (ctDNA) on treatment are associated with improved overall survival (OS) in patients with advanced non-small cell lung cancer (aNSCLC) treated with immunotherapy or chemotherapy.
“ctDNA continues to hold promise as an early endpoint for regulatory decision-making. This work builds on growing evidence that reductions in ctDNA on-treatment are associated with improved OS and begins to address questions about plasma collection timing and how to define molecular response,” Hillary Andrews, Director of Regulatory and Research Partnerships at Friends.
The aggregate analysis, published in the Journal for ImmunoTherapy of Cancer, pooled data from four randomized clinical trials involving 918 patients treated with anti-PD(L)1 therapy (with or without chemotherapy) or chemotherapy alone. Researchers assessed outcomes associated with ctDNA molecular response (MR) vs non-molecular response (nMR) using three MR thresholds (≥50% reduction, ≥90%, and 100% clearance) at two post-treatment timepoints: an early window (up to 7 weeks) and a later window (7-13 weeks).
“Our findings suggest that across all three molecular response thresholds, changes in ctDNA are associated with OS in patients with advanced non-small cell lung cancer treated with either anti-PD(L)1 or chemotherapy. Additional research is planned as part of the ctMoniTR project to evaluate molecular response thresholds across different tumor types and treatment modalities,” Nevine Zariffa, NMD Group Founder and Friends’ consultant for the ctMoniTR Project.
Trial-level meta-analyses and prospective studies will also be essential next steps to advancing and validating ctDNA as an early endpoint for regulatory decision making.
Read the publication: http://dx.doi.org/10.1136/jitc-2025-012454.
Manuscript Authors
Hillary S. Andrews1, Nevine Zariffa2, Katherine K. Nishimura3, Yu Deng4, Megan Eisele3, Joe Ensor5, Carin R. Espenschied6, David Fabrizio7, Emily M. Goren3, Vincent Haddad9, Minetta C. Liu5, Dimple Modi8, Achim K. Moesta8, Katie Quinn6, Adam Rosenthal3, Diana Merino Vega9, Wei Zou4, Antje Hoering3, Mark D. Stewart1, Jeff D. Allen1
Affiliations
1Friends of Cancer Research, 2NMD Group Inc., 3Cancer Research And Biostatistics, 4Genentech, 5Natera Inc., 6Guardant Health, Inc., 7Foundation Medicine, 8Regeneron Pharmaceuticals, Inc., 9AstraZeneca
Acknowledgements
A special thank you to the ctMoniTR Statistical Working Group members and the Broad Working Group members for making this research partnership and publication possible: Agilent Technologies, AstraZeneca, Bayer, Biodesix, Bio-Rad Laboratories, Inc., Boehringer Ingelheim, Cancer Research And Biostatistics (CRAB), EMD Serono, Inc. (Merck KGaA), European Organization for Research and Treatment of Cancer (EORTC), Foundation Medicine, Inc., Genentech, Inc., Genmab, Guardant Health, Inc., Illumina, Inc., Johns Hopkins University School of Medicine, Loxo@Lilly, MD Anderson Cancer Center, Molecular Characterization Laboratory (MoCha) at Frederick National Laboratory, Natera, Inc., NMD Group LLC, Novartis AG, Pfizer, Princess Margaret Cancer Centre, Regeneron Pharmaceuticals, Inc., Roche Diagnostics, Takeda Pharmaceutical Company, the U.S. Food and Drug Administration (FDA), and Xencor.
Learn more about Friends’ ctMoniTR portfolio and the projects, events and next steps that have led to this important publication here.