Circulating tumour DNA predicts response to anti-PD1 antibodies in metastatic melanoma
Open accessAbstract
Background Programmed death 1 (PD1) inhibitors are now a foundation of medical management of metastatic melanoma. This study sought to determine whether circulating tumour DNA (ctDNA) provides useful early response and prognostic information.Patients and methods We evaluated the relationship between pre-treatment and early on treatment ctDNA and outcome in melanoma patients treated with PD1 inhibitors alone or in combination with ipilimumab.Results ctDNA was detected in 40/76 patients (53%) at baseline, and correlated with stage, LDH levels, disease volume and ECOG performance. RECIST response was 72% (26/36) in group A (undetectable ctDNA at baseline), 77% (17/22) in group B (elevated ctDNA at baseline but undetectable within 12 weeks of therapy) and 6% (1/18) in group C (elevated ctDNA at baseline and remained elevated during treatment). The median PFS was not reached in groups A and B and was 2.7 months for group C [hazard ratio (HR) 0.09; P < 0.001 for group A versus C, and 0.16; P < 0.001 for group B versus C]. The median OS was not reached for groups A and B and was 9.2 months for group C (HR 0.02; P < 0.001 for group A versus C and 0.14; P < 0.001 for group B versus C). The poor outcome measures associated with group C remained significant in multivariate analysis adjusted for LDH, performance status, tumour stage and disease volume. The predictive value for ctDNA for response was confirmed in a separate validation cohort (n = 29, P < 0.01).Conclusion Longitudinal assessment of ctDNA in metastatic melanoma patients receiving treatment with PD1 inhibitors is an accurate predictor of tumour response, PFS and OS. Patients who had a persistently elevated ctDNA on therapy had a poor prognosis, and this may guide combination and sequencing of subsequent therapies.
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Serum ctDNA is an attractive biomarker before and during immune checkpoint treatment.
“A recent study in advanced stage melanoma patients treated with anti-PD-1 (alone or in combination with anti-CTLA-4) showed high treatment response rates in individuals that were ctDNA negative prior to or after treatment (107), making serum ctDNA an attractive biomarker before and during immune checkpoint treatment.”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [107]
In advanced stage melanoma patients treated with anti-PD-1 (alone or with anti-CTLA-4), high treatment response rates were seen in individuals who were ctDNA negative prior to or after treatment.
“A recent study in advanced stage melanoma patients treated with anti-PD-1 (alone or in combination with anti-CTLA-4) showed high treatment response rates in individuals that were ctDNA negative prior to or after treatment (107), making serum ctDNA an attractive biomarker before and during immune checkpoint treatment.”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [107]
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- Authors
- Lee, J. H., Long, G. V., Boyd, S., Lo, S., Menzies, A. M., Tembe, V., Guminski, A., Jakrot, V., Scolyer, R. A., Mann, G. J., Kefford, R. F., Carlino, M. S., & Rizos, H.
- Affiliations
- The University of Sydney (AU)
- Macquarie University (AU)
- Melanoma Institute Australia (AU)
- Royal Prince Alfred Hospital (AU)
- Corresponding author
- Rizos, H.
- ORCID
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 28
- Issue
- 5
- Pages
- 1130-1136
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2588078993
- Cited by
- 333
- References
- 25
- Citations by year
- 2026: 22 · 2025: 21 · 2024: 16 · 2023: 52 · 2022: 28 · 2021: 51 · 2020: 48 · 2019: 43 · 2018: 39 · 2017: 12
- FWCI
- 17.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council (1093017 and 1130423)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- circulating tumor DNA, metastatic melanoma, PD-1 inhibitors, ipilimumab, treatment response prediction, prognostic factors, progression-free survival, overall survival, longitudinal ctDNA monitoring, immune checkpoint inhibitors
- MeSH terms
- Circulating Tumor DNA, Ipilimumab, Aged, Antibodies, Anti-Idiotypic, Female, Humans, Male, Melanoma, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Prognosis, Biomarkers, Tumor, Neoplasms, Second Primary, Disease-Free Survival, Programmed Cell Death 1 Receptor
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