A Phase II Study of Osimertinib in Patients with Advanced-Stage Non-Small Cell Lung Cancer following Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) Therapy with EGFR and T790M Mutations Detected in Plasma Circulating Tumour DNA (PLASMA Study)
Issued Date
2023-10-01
Resource Type
eISSN
20726694
Scopus ID
2-s2.0-85175055202
Journal Title
Cancers
Volume
15
Issue
20
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cancers Vol.15 No.20 (2023)
Suggested Citation
Ang Y.L.E., Zhao X., Reungwetwattana T., Cho B.C., Liao B.C., Yeung R., Loong H.H., Kim D.W., Yang J.C.H., Lim S.M., Ahn M.J., Lee S.H., Suwatanapongched T., Kongchauy K., Ou Q., Yu R., Tai B.C., Goh B.C., Mok T.S.K., Soo R.A. A Phase II Study of Osimertinib in Patients with Advanced-Stage Non-Small Cell Lung Cancer following Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) Therapy with EGFR and T790M Mutations Detected in Plasma Circulating Tumour DNA (PLASMA Study). Cancers Vol.15 No.20 (2023). doi:10.3390/cancers15204999 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/90920
Title
A Phase II Study of Osimertinib in Patients with Advanced-Stage Non-Small Cell Lung Cancer following Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) Therapy with EGFR and T790M Mutations Detected in Plasma Circulating Tumour DNA (PLASMA Study)
Author's Affiliation
Yonsei Cancer Hospital
National Taiwan University Hospital
Samsung Medical Center, Sungkyunkwan university
National University of Singapore
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Chinese University of Hong Kong
Seoul National University College of Medicine
Pamela Youde Nethersole Eastern Hospital
Nanjing Geneseeq Technology Inc.
National University Cancer Institute
National Taiwan University Hospital
Samsung Medical Center, Sungkyunkwan university
National University of Singapore
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Chinese University of Hong Kong
Seoul National University College of Medicine
Pamela Youde Nethersole Eastern Hospital
Nanjing Geneseeq Technology Inc.
National University Cancer Institute
Other Contributor(s)
Abstract
Epidermal growth factor receptor (EGFR) T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second generation (1G/2G) EGFR tyrosine kinase inhibitors (TKIs) and are sensitive to Osimertinib. Tissue sampling is the gold-standard modality of T790M testing, but it is invasive. We evaluated the efficacy of Osimertinib in patients with EGFR mutant NSCLC and T790M in circulating tumour DNA (ctDNA). PLASMA is a prospective, open-label, multicentre single-arm Phase II study. Patients with advanced NSCLC harbouring sensitizing EGFR and T790M mutations in plasma at progression from ≥one 1G/2G TKI were treated with 80 mg of Osimertinib daily until progression. The primary endpoint was the objective response rate (ORR); the secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and toxicities. Plasma next-generation sequencing was performed to determine Osimertinib resistance mechanisms and assess serial ctDNA. A total of 110 patients from eight centres in five countries were enrolled from 2017 to 2019. The median follow-up duration was 2.64 (IQR 2.44–3.12) years. The ORR was 50.9% (95% CI 41.2–60.6) and the DCR was 84.5% (95% CI 76.4–90.7). Median PFS was 7.4 (95% CI 6.0–9.3) months; median OS was 1.63 (95% CI 1.35–2.16) years. Of all of the patients, 76% had treatment-related adverse events (TRAEs), most commonly paronychia (22.7%); 11% experienced ≥ Grade 3 TRAEs. The ctDNA baseline load and dynamics were prognostic. Osimertinib is active in NSCLC harbouring sensitizing EGFR and T790M mutations in ctDNA testing post 1G/2G TKIs.