Tags

Type your tag names separated by a space and hit enter

Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA.
Ann Oncol. 2017 04 01; 28(4):784-790.AO

Abstract

Background

Approximately 50% of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by the T790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients.

Material and methods

ctDNA T790M mutational status was assessed by Inivata InVision™ (eTAm-Seq™) assay in 48 EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKIs without a tissue biopsy between April 2015 and April 2016. Progressing T790M-positive NSCLC patients received osimertinib (80 mg daily). The objectives were to assess the response rate to osimertinib according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, the progression-free survival (PFS) on osimertinib, and the percentage of T790M positive in ctDNA.

Results

The ctDNA T790M mutation was detected in 50% of NSCLC patients. Among assessable patients, osimertinib gave a partial response rate of 62.5% and a stable disease rate of 37.5%. All responses were confirmed responses. After median follow up of 8 months, median PFS by RECIST criteria was not achieved (95% CI: 4-NA), with 6- and 12-months PFS of 66.7% and 52%, respectively.

Conclusion(s)

ctDNA from liquid biopsy can be used as a surrogate marker for T790M in tumour tissue.

Authors+Show Affiliations

Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.Radiology, Gustave Roussy, Université Paris-Saclay, Villejuif, France.Translational Research Laboratory, AMMICA, INSERM US23/CNRS UNS3655, Gustave Roussy, Villejuif, France.Translational Research Laboratory, AMMICA, INSERM US23/CNRS UNS3655, Gustave Roussy, Villejuif, France.Inivata Ltd, Cambridge, UK.Inivata Ltd, Cambridge, UK.Inivata Ltd, Cambridge, UK.Inivata Ltd, Cambridge, UK. Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.Inivata Ltd, Cambridge, UK.Inivata Ltd, Cambridge, UK.Inivata Ltd, Cambridge, UK. Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK. Cambridge Cancer Centre, Cambridge, UK.Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France.Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France. University Paris-Sud and Gustave Roussy Cancer Campus, Villejuif, France.Department of Medical Oncology, Gustave Roussy Cancer Campus, Villejuif, France. University Paris-Sud and Gustave Roussy Cancer Campus, Villejuif, France.

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

28104619

Citation

Remon, J, et al. "Osimertinib Benefit in EGFR-mutant NSCLC Patients With T790M-mutation Detected By Circulating Tumour DNA." Annals of Oncology : Official Journal of the European Society for Medical Oncology, vol. 28, no. 4, 2017, pp. 784-790.
Remon J, Caramella C, Jovelet C, et al. Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA. Ann Oncol. 2017;28(4):784-790.
Remon, J., Caramella, C., Jovelet, C., Lacroix, L., Lawson, A., Smalley, S., Howarth, K., Gale, D., Green, E., Plagnol, V., Rosenfeld, N., Planchard, D., Bluthgen, M. V., Gazzah, A., Pannet, C., Nicotra, C., Auclin, E., Soria, J. C., & Besse, B. (2017). Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA. Annals of Oncology : Official Journal of the European Society for Medical Oncology, 28(4), 784-790. https://doi.org/10.1093/annonc/mdx017
Remon J, et al. Osimertinib Benefit in EGFR-mutant NSCLC Patients With T790M-mutation Detected By Circulating Tumour DNA. Ann Oncol. 2017 04 1;28(4):784-790. PubMed PMID: 28104619.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA. AU - Remon,J, AU - Caramella,C, AU - Jovelet,C, AU - Lacroix,L, AU - Lawson,A, AU - Smalley,S, AU - Howarth,K, AU - Gale,D, AU - Green,E, AU - Plagnol,V, AU - Rosenfeld,N, AU - Planchard,D, AU - Bluthgen,M V, AU - Gazzah,A, AU - Pannet,C, AU - Nicotra,C, AU - Auclin,E, AU - Soria,J C, AU - Besse,B, PY - 2016/10/17/received PY - 2017/1/21/pubmed PY - 2017/5/4/medline PY - 2017/1/21/entrez KW - EGFR mutation KW - T790M KW - ctDNA liquid biopsies KW - lung cancer KW - osimertinib SP - 784 EP - 790 JF - Annals of oncology : official journal of the European Society for Medical Oncology JO - Ann. Oncol. VL - 28 IS - 4 N2 - Background: Approximately 50% of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by the T790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients. Material and methods: ctDNA T790M mutational status was assessed by Inivata InVision™ (eTAm-Seq™) assay in 48 EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKIs without a tissue biopsy between April 2015 and April 2016. Progressing T790M-positive NSCLC patients received osimertinib (80 mg daily). The objectives were to assess the response rate to osimertinib according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, the progression-free survival (PFS) on osimertinib, and the percentage of T790M positive in ctDNA. Results: The ctDNA T790M mutation was detected in 50% of NSCLC patients. Among assessable patients, osimertinib gave a partial response rate of 62.5% and a stable disease rate of 37.5%. All responses were confirmed responses. After median follow up of 8 months, median PFS by RECIST criteria was not achieved (95% CI: 4-NA), with 6- and 12-months PFS of 66.7% and 52%, respectively. Conclusion(s): ctDNA from liquid biopsy can be used as a surrogate marker for T790M in tumour tissue. SN - 1569-8041 UR - https://www.unboundmedicine.com/medline/citation/28104619/Osimertinib_benefit_in_EGFR_mutant_NSCLC_patients_with_T790M_mutation_detected_by_circulating_tumour_DNA_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0923-7534(19)32080-0 DB - PRIME DP - Unbound Medicine ER -