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)
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Trial Patients
2.2. Trial Design, Treatment and Assessments
2.3. Trial Endpoints
2.4. Trial Oversight
2.5. Cell-Free DNA Extract, Library Construction and Targeted Panel Next-Generation Sequencing
2.6. Sequence Data Processing and Mutation Calling
2.7. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Efficacy
3.3. Adverse Events and Dosing Adjustments
3.4. Exploratory Endpoints
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
References
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Characteristics | All Patients (n = 110) |
---|---|
Median age (range), years | 65.8 (40.7–93.7) |
Gender (%) | |
Male | 54 (49.1) |
Female | 56 (50.9) |
Region of participation (%) | |
Hong Kong | 12 (10.9) |
Korea | 22 (20.0) |
Singapore | 30 (27.3) |
Taiwan | 15 (13.6) |
Thailand | 31 (28.2) |
Smoking status (%) | |
Never smoker | 78 (70.9) |
Ex-smoker | 26 (23.6) |
Current smoker | 6 (5.5) |
ECOG performance status (%) | |
0 | 25 (22.7) |
1 | 75 (68.2) |
2 | 10 (9.1) |
CNS metastasis (%) | 36 (33.3) |
Metastasis (%) | 104 (94.6) |
Clinical staging at enrolment (%) | |
Stage III | 6 (5.5) |
Stage IV | 104 (94.6) |
Prior therapy (%) | |
Chemotherapy | 30 (27.3) |
Radiotherapy | 54 (49.1) |
Surgery | 38 (34.6) |
Prior TKI (%) | |
Afatinib | 20 (18.2) |
Erlotinib | 30 (27.2) |
Gefitinib | 60 (54.6) |
EGFR mutation status (%) | |
Exon 19 deletion | 66 (60.0) |
L858R | 44 (40.0) |
Best Response | All Patients (n = 110) | CNS Metastasis (n = 36) |
---|---|---|
CR | 1 (0.9) | 0 (0) |
PR | 55 (50.0) | 22 (61.1) |
SD | 37 (33.6) | 10 (27.8) |
PD | 10 (9.1) | 3 (8.3) |
Not evaluable | 7 (6.4) | 1 (2.8) |
ORR (95% CI) | ||
Intention to treat (ITT) | 50.9 (41.2–60.2) | 61.1 (43.5–76.9) |
Modified intention to treat (mITT) | 54.4 (44.3–64.2) | 62.9 (44.9–78.5) |
Median DoR (95% CI), months | 7.2 (3.6–11.0) | 3.6 (1.9–13.1) |
DCR (95% CI) | ||
ITT | 84.5 (76.4–90.7) | 88.9 (73.9–96.9) |
mITT | 90.3 (82.9–95.2) | 91.4 (76.9–98.2) |
TRAE | All Grades (n = 110) | Grade 3 |
---|---|---|
Paronychia | 25 (22.7%) | 0 |
Dry skin | 23 (20.9%) | 0 |
Rash | 15 (13.6%) | 0 |
Diarrhoea | 14 (12.7%) | 0 |
Pruritis | 11 (10.0%) | 1 (0.9%) |
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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.; et al. 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 2023, 15, 4999. https://doi.org/10.3390/cancers15204999
Ang YLE, Zhao X, Reungwetwattana T, Cho B-C, Liao B-C, Yeung R, Loong HH, Kim D-W, Yang JC-H, Lim SM, et al. 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. 2023; 15(20):4999. https://doi.org/10.3390/cancers15204999
Chicago/Turabian StyleAng, Yvonne L. E., Xiaotian Zhao, Thanyanan Reungwetwattana, Byoung-Chul Cho, Bin-Chi Liao, Rebecca Yeung, Herbert H. Loong, Dong-Wan Kim, James Chih-Hsin Yang, Sun Min Lim, and et al. 2023. "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 15, no. 20: 4999. https://doi.org/10.3390/cancers15204999