Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab.
Journal
Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
07
03
2020
accepted:
26
06
2020
entrez:
5
2
2022
pubmed:
1
9
2020
medline:
15
4
2022
Statut:
ppublish
Résumé
Immune checkpoint blockade (ICB) provides clinical benefit to a subset of patients with cancer. However, existing biomarkers do not reliably predict treatment response across diverse cancer types. Limited data exist to show how serial circulating tumor DNA (ctDNA) testing may perform as a predictive biomarker in patients receiving ICB. We conducted a prospective phase II clinical trial to assess ctDNA in five distinct cohorts of patients with advanced solid tumors treated with pembrolizumab (NCT02644369). We applied bespoke ctDNA assays to 316 serial plasma samples obtained at baseline and every three cycles from 94 patients. Baseline ctDNA concentration correlated with progression-free survival, overall survival, clinical response and clinical benefit. This association became stronger when considering ctDNA kinetics during treatment. All 12 patients with ctDNA clearance during treatment were alive with median 25 months follow up. This study demonstrates the potential for broad clinical utility of ctDNA-based surveillance in patients treated with ICB.
Identifiants
pubmed: 35121950
doi: 10.1038/s43018-020-0096-5
pii: 10.1038/s43018-020-0096-5
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Biomarkers
0
Circulating Tumor DNA
0
pembrolizumab
DPT0O3T46P
Banques de données
ClinicalTrials.gov
['NCT02644369']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
873-881Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020. The Author(s), under exclusive licence to Springer Nature America, Inc.
Références
Bedognetti, D. et al. Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop. J. Immunother. Cancer 7, 131 (2019).
doi: 10.1186/s40425-019-0602-4
Hause, R. J., Pritchard, C. C., Shendure, J. & Salipante, S. J. Classification and characterization of microsatellite instability across 18 cancer types. Nat. Med. 22, 1342–1350 (2016).
doi: 10.1038/nm.4191
Jenkins, R. W., Thummalapalli, R., Carter, J., Canadas, I. & Barbie, D. A. Molecular and genomic determinants of response to immune checkpoint inhibition in cancer. Annu. Rev. Med. 69, 333–347 (2018).
doi: 10.1146/annurev-med-060116-022926
Rizvi, N. A. et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348, 124–128 (2015).
doi: 10.1126/science.aaa1348
Snyder, A. et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N. Engl. J. Med. 371, 2189–2199 (2014).
doi: 10.1056/NEJMoa1406498
Tumeh, P. C. et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 515, 568–571 (2014).
doi: 10.1038/nature13954
Gibney, G. T., Weiner, L. M. & Atkins, M. B. Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol. 17, e542–e551 (2016).
doi: 10.1016/S1470-2045(16)30406-5
Eisenhauer, E. A. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer 45, 228–247 (2009).
doi: 10.1016/j.ejca.2008.10.026
Wolchok, J. D. et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin. Cancer Res. 15, 7412–7420 (2009).
doi: 10.1158/1078-0432.CCR-09-1624
Ribas, A., Chmielowski, B. & Glaspy, J. A. Do we need a different set of response assessment criteria for tumor immunotherapy? Clin. Cancer Res. 15, 7116–7118 (2009).
doi: 10.1158/1078-0432.CCR-09-2376
Corcoran, R. B. & Chabner, B. A. Application of cell-free DNA analysis to cancer treatment. N. Engl. J. Med. 379, 1754–1765 (2018).
doi: 10.1056/NEJMra1706174
Cabel, L. et al. Clinical potential of circulating tumour DNA in patients receiving anticancer immunotherapy. Nat. Rev. Clin. Oncol. 15, 639–650 (2018).
doi: 10.1038/s41571-018-0074-3
Anagnostou, V. et al. Dynamics of tumor and immune responses during immune checkpoint blockade in non-small cell lung cancer. Cancer Res. 79, 1214–1225 (2019).
doi: 10.1158/0008-5472.CAN-18-1127
Cabel, L. et al. Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study. Ann. Oncol. 28, 1996–2001 (2017).
doi: 10.1093/annonc/mdx212
Giroux Leprieur, E. et al. Circulating tumor DNA evaluated by Next-Generation Sequencing is predictive of tumor response and prolonged clinical benefit with nivolumab in advanced non-small cell lung cancer. Oncoimmunology. 7, e1424675 (2018).
doi: 10.1080/2162402X.2018.1424675
Goldberg, S. B. et al. Early assessment of lung cancer immunotherapy response via circulating tumor DNA. Clin. Cancer Res. 24, 1872–1880 (2018).
doi: 10.1158/1078-0432.CCR-17-1341
Gray, E. S. et al. Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma. Oncotarget 6, 42008–42018 (2015).
doi: 10.18632/oncotarget.5788
Lee, J. H. et al. Circulating tumour DNA predicts response to anti-PD1 antibodies in metastatic melanoma. Ann. Oncol. 28, 1130–1136 (2017).
doi: 10.1093/annonc/mdx026
Lee, J. H. et al. Association between circulating tumor DNA and pseudoprogression in patients with metastatic melanoma treated with anti-programmed cell death 1 antibodies. JAMA Oncol. 4, 717–721 (2018).
doi: 10.1001/jamaoncol.2017.5332
Raja, R. et al. Early reduction in ctDNA predicts survival in patients with lung and bladder cancer treated with durvalumab. Clin. Cancer Res. 24, 6212–6222 (2018).
doi: 10.1158/1078-0432.CCR-18-0386
Moding, E. J. et al. Circulating tumor DNA dynamics predict benefit from consolidation immunotherapy in locally advanced non-small-cell lung cancer. Nat. Cancer 1, 176–183 (2020).
doi: 10.1038/s43018-019-0011-0
Clouthier, D. L. et al. An interim report on the investigator-initiated phase 2 study of pembrolizumab immunological response evaluation (INSPIRE). J. Immunother. Cancer 7, 72 (2019).
doi: 10.1186/s40425-019-0541-0
Coombes, R. C. et al. Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence. Clin. Cancer Res. 25, 4255–4263 (2019).
doi: 10.1158/1078-0432.CCR-18-3663
Magbanua, M. J. M. et al. Circulating tumor DNA in neoadjuvant treated breast cancer reflects response and survival. Preprint at medRxiv https://doi.org/10.1101/2020.02.03.20019760 (2020).
Christensen, E. et al. Early detection of metastatic relapse and monitoring of therapeutic efficacy by ultra-deep sequencing of plasma cell-free DNA in patients with urothelial bladder carcinoma. J. Clin. Oncol. 37, 1547–1557 (2019).
doi: 10.1200/JCO.18.02052
Reinert, T. et al. Analysis of of plasma cell-free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer. JAMA Oncol. 5, 1124–1131 (2019).
doi: 10.1001/jamaoncol.2019.0528
Newman, A. M. et al. Integrated digital error suppression for improved detection of circulating tumor DNA. Nat. Biotechnol. 34, 547–555 (2016).
doi: 10.1038/nbt.3520
Koboldt, D. C. et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res. 22, 568–576 (2012).
doi: 10.1101/gr.129684.111
McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303 (2010).
doi: 10.1101/gr.107524.110
Cibulskis, K. et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat. Biotechnol. 31, 213–219 (2013).
doi: 10.1038/nbt.2514
Lai, Z. et al. VarDict: a novel and versatile variant caller for next-generation sequencing in cancer research. Nucleic Acids Res. 44, e108 (2016).
doi: 10.1093/nar/gkw227
Salipante, S. J., Scroggins, S. M., Hampel, H. L., Turner, E. H. & Pritchard, C. C. Microsatellite instability detection by next generation sequencing. Clin. Chem. 60, 1192–1199 (2014).
doi: 10.1373/clinchem.2014.223677
McGranahan, N. et al. Clonal status of actionable driver events and the timing of mutational processes in cancer evolution. Sci. Transl. Med. 7, 283ra254 (2015).
doi: 10.1126/scitranslmed.aaa1408