At the European Society for Medical Oncology (ESMO) 2025 congress, late-breaking data from the PATHFINDER 2 study were presented by Dr Nima Nabavizadeh (Associate Professor of Radiation Medicine, School of Medicine, Oregon Health & Science University, Portland, OR, USA). The study centred on the Galleri multi-cancer early detection (MCED) test, which uses DNA methylation profiling, next-generation sequencing and machine learning to predict cancer signals and their tissue of origin. Involving nearly 36,000 participants aged 50 and older, PATHFINDER 2 demonstrated strong safety, high positive predictive value, and markedly improved early cancer detection compared with standard screening – reinforcing MCED testing’s complementary role alongside established cancer screening programs.
The late-breaking abstract, ‘Safety and Performance of a Multi-Cancer Early Detection (MCED) Test in an Intended-Use Population: Initial Results from the Registrational PATHFINDER 2 Study’ (LBA64) was presented at the European Society for Medical Oncology (ESMO) congress on 17th-21st October 2025 in Berlin, Germany.
Q1. What are the key functions of the Galleri multi-cancer early detection (MCED) test?
The Galleri MCED test analyzes circulating cell-free DNA methylation profiles to predict a cancer signal using next-generation sequencing and machine learning. When a cancer signal is detected, the test provides a predicted tissue of origin, helping providers focus diagnostic evaluation where cancer is most likely to be found.
Q2. Can you summarize the design and eligibility criteria for the PATHFINDER 2 study, and how it builds on the original PATHFINDER study?
PATHFINDER 2 is a registrational study evaluating the safety and efficacy of the Galleri test in its intended use population. We enrolled nearly 36,000 participants across 32 North American healthcare systems over 32 months. Eligible participants were aged 50 or older, had no clinical suspicion of cancer, and no history of cancer or cancer therapy within the past three years.
The study builds on the original PATHFINDER trial, which included around 6,000 participants. PATHFINDER 2 represents a next-generation evaluation, with a larger, more representative population reflecting a realistic mix of cancers.
Q3. What were the overall cancer detection rates?
In our initial analysis of 25,000 participants with at least 12 months of follow-up, the cancer signal detection rate was just under 1%. Among participants with a positive test result, the positive predictive value (PPV) was 62%, meaning six out of ten had a confirmed cancer diagnosis after targeted evaluation.
Q4. What are the key takeaways from the initial results of PATHFINDER 2?
First, the Galleri test detected significantly more screen-detected cancers than current US screening methods. Of the 329 cancers identified within 12 months, 61% were screen-detected – far higher than the 14% detected by standard screenings like mammography, colonoscopy, lung and cervical cancer screening.
Overall, the test increased the number of screen-detected cancers by more than sevenfold. Importantly, most cancers detected were early-stage and included those without established screening guidelines, demonstrating the test’s potential to address an unmet need.
Q5. How do PATHFINDER 2 and the UK NHS-Galleri trials relate, and how do you see MCED tests fitting with current screening programs?
PATHFINDER 2 is the largest single-arm interventional US study designed for FDA registration. The NHS-Galleri trial in the UK is a randomized study of 140,000 participants, comparing standard-of-care screening with or without the Galleri test. I see MCED tests complementing existing screenings – mammography, colonoscopy, lung and cervical cancer detection – while also addressing cancers for which no screening currently exists. They are an important addition, rather than a replacement, offering earlier detection and guiding more targeted diagnostic evaluations.
Disclosure: Nima Nabavizadeh is a consultant for GRAIL and Quattro consulting. He is a member of the Advisory Board for GRAIL, and has received honoraria/honorarium from Roche and MJH life sciences.
This content has been developed independently by Touch Medical Media for touchONCOLOGY. It is not affiliated with the European Society for Medical Oncology (ESMO). Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Cite: PATHFINDER 2: Galleri MCED test detects early-stage cancers beyond standard screening. touchONCOLOGY. November 11th, 2025
Related content
- ESMO25 Late-breaker: ENGOT-ov65/KEYNOTE-B96 shows survival benefit in platinum-resistant ovarian cancer
- ESMO25 Late-breaker: VIKTORIA-1 triplet and doublet combinations improve PFS in HR+/HER2– PIK3CA wild-type breast cancer
- ESMO25 Presidential Late-breaker: KEYNOTE-905 delivers breakthrough results in cisplatin-ineligible MIBC
