Abstract 266P
Background
We analysed dynamic mutation profiles of next-generation sequencing (NGS) T790M+ advanced non-small cell lung cancer (NSCLC) patients from an open-label, multicentre study (ADELOS, NCT02997501) in China.
Methods
T790M+ patients pre-treated with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), received osimertinib 80 mg/day orally till disease progression (PD). Progression-free survival (PFS) was defined as the time from treatment to PD/death. NGS (168-gene panel) was used as one of four methods to identify T790M at baseline and monitor mutation status in circulating tumour DNA (ctDNA) from different timepoints.
Results
Among 167 T790M+ patients receiving osimertinib, 129 were T790M+ by NGS (NGS+) and 89 were T790M+ by Cobas (Cobas+) at baseline. Median PFS (mPFS) (95% CI) of NGS+ and Cobas+ was 11.0 (9.5-13.8) and 10.6 (8.5-13.8) months, respectively, while 40 T790M- by Cobas in NGS+ had mPFS of 11.3 (8.3-NA) months. In NGS+, 62 had EGFR only (19del, L858R or any uncommon mutation), 54 had tumour suppressor only (TP53, RB1 and PTEN) and 13 had multiple driver (KRAS, MET amp, BRAF V600E, HER2 amp, ROS1 fusion, ALK fusion and RET fusion) with mPFS of 15.0 (9.72-NE), 9.1 (7.06-10.97) and 7.6 (2.23-15.41) months, respectively. T790M/EGFR mutations (T790M, G719X, L858R, 19del, L816Q, 20ins, S768I, C797S) clearance at treatment week 6 and best response and presence of T790M at PD were associated with longer PFS (Table). Table: 266P
mPFS by EGFR/T790M mutation status
| T790M+ | T790M- | P-value | EGFR+ | EGFR- | P-value | ||
| Months (95% CI) | Treatment Week 6 | 7.5 (4.0-15.3) | 11.0 (9.5-15.0) | 0.0441 | 6.7 (4.5-8.5) | 15.0 (11.1-NA) | <0.0001 |
| Best response | 6.7 (1.2-12.4) | 11.0 (9.5-15.0) | 0.0026 | 6.4 (4.5-8.5) | 15.0 (10.7-NA) | <0.0001 | |
| Before PD | 8.7 (4.0-13.8) | 8.3 (6.4-8.5) | 0.3337 | 8.2 (6.4-8.5) | 9.7 (4.6-11.1) | 0.8225 | |
| PD | 12.4 (6.8-15.1) | 8.3 (5.4-9.5) | 0.0264 | 8.4 (6.8-10.5) | 9.5 (2.9-11.0) | 0.2687 |
Conclusions
Co-mutation (multiple driver and tumour suppressor) at baseline and early clearance of T790M/EGFR mutations were corelated with efficacy and could be prognostic factors of osimertinib treatment. NGS might increase the population base that could benefit from osimertinib due to detection of low frequency mutations.
Clinical trial identification
NCT02997501.
Editorial acknowledgement
Indegene Pvt. Ltd.
Legal entity responsible for the study
Xuchao Zhang.
Funding
AstraZeneca China.
Disclosure
All authors have declared no conflicts of interest.
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