Can Quantitative Measures of T790M Allelic Fraction Predict Survival Outcomes in Patients Receiving Osimertinib? Observations From an Early Access Programme |
| |
| Authors: | OSH Chan VHF Lee SF Nyaw MTY Kam KWC Lee KC Lam |
| |
| Institution: | 1. Hong Kong Integrated Oncology Centre, Hong Kong, China;2. Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China;3. Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;4. Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong, China;5. Department of Clinical Oncology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Shatin, Hong Kong, China;1. University of Toronto, Department of Radiation Oncology, Toronto, Ontario, Canada;2. University of Calgary, Department of Radiation Oncology, Calgary, Alberta, Canada;3. Sunnybrook Hospital, Toronto, Ontario, Canada;1. Cancer Centre Belfast City Hospital, Belfast Health & Social Care Trust, Belfast, Northern Ireland, UK;2. Patrick G Johnston Centre for Cancer Research, Queen''s University Belfast, Belfast, Northern Ireland, UK;3. Centre for Medical Education, Queen''s University Belfast, Belfast, Northern Ireland, UK;4. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia;1. Radiotherapy Department, University College London Hospital NHS Foundation Trust, London, UK;2. Radiotherapy Physics, University College London Hospital NHS Foundation Trust, London, UK;3. Department of Medical Physics and Bioengineering, University College London, London, UK;1. Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK;2. Royal College of Radiologists, London, UK;1. University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK;2. University of Keele, Keele, UK;3. University of Cambridge, Cambridge, UK;4. Royal College of Radiologists, London, UK;5. The Royal Marsden NHS Foundation Trust, London, UK |
| |
| Abstract: | AimsMultiple studies have shown conflicting results on the correlation between the EGFR T790M quantitative level and survival outcomes in osimertinib-treated patients. We sought to validate such correlations using data from an osimertinib early access programme (EAP) providing access for metastatic non-small cell lung cancer patients with limited treatment options.Patients and methodsThis observational, multicentre, retrospective analysis included EAP participants who received osimertinib until disease progression, intolerable toxicities or death. Digital droplet polymerase chain reaction-based quantitative plasma genotyping was carried out upon disease progression and data were analysed to explore the relationships between T790M mutant allele fraction (MAF), T790M copy number, MAF ratio and post-osimertinib overall survival. Real-world treatment outcomes and safety were also evaluated.ResultsData from 156 EAP participants were analysed (median follow-up 37.7 months). The median age was 62 years, 62.2% were women, 79.5% were never-smokers, 60.9% had Eastern Cooperative Oncology Group performance status 0/1. In patients with available plasma data (n = 114), T790M MAF (%) showed no significant relationships with overall survival (hazard ratio 1.02; 95% confidence interval 0.99–1.04) or time to treatment discontinuation (TTD) (hazard ratio 1.01; 95% confidence interval 0.98–1.04). Absolute T790M copy number and T790M to activating EGFR mutation MAF ratio also showed no prognostic value. The investigator-assessed response rate was 42.3% and the disease control rate was 85.5%. The median TTD was 15.8 (95% confidence interval 12.5–18.5) months and the median overall survival was 22.3 (95% confidence interval 18.6–26.1) months.ConclusionT790M MAF did not correlate with TTD or overall survival in this EAP cohort but limitations should not be overlooked. Observed survival outcomes and the toxicity profile were consistent with data from other real-world series. |
| |
| Keywords: | Early access programme EGFT-mutant NSCLC mutant allele fraction osimertinib |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
