Patterns of progression on osimertinib in EGFR T790M positive NSCLC: A Swiss cohort study

S Schmid, D Klingbiel, S Aeppli, C Britschgi… - Lung Cancer, 2019 - Elsevier
S Schmid, D Klingbiel, S Aeppli, C Britschgi, O Gautschi, M Pless, S Rothschild…
Lung Cancer, 2019Elsevier
Introduction Osimertinib is an EGFR tyrosine kinase inhibitor (TKI) with antitumor activity in
non-small cell lung cancer (NSCLC) with EGFR T790 M mutations. The incidence of oligo-
progression (PD) on osimertinib is unknown. Methods We retrospectively analyzed 50 pre-
treated EGFR T790M-positive NSCLC patients treated with osimertinib at seven Swiss
centers. Oligo-PD was defined as PD in≤ 5 lesions. Mutational profiling of pre-and post-
osimertinib tumor samples was performed. Results Median age was 62 years (37–89), 64 …
Introduction
Osimertinib is an EGFR tyrosine kinase inhibitor (TKI) with antitumor activity in non-small cell lung cancer (NSCLC) with EGFR T790 M mutations. The incidence of oligo-progression (PD) on osimertinib is unknown.
Methods
We retrospectively analyzed 50 pre-treated EGFR T790M-positive NSCLC patients treated with osimertinib at seven Swiss centers. Oligo-PD was defined as PD in ≤ 5 lesions. Mutational profiling of pre- and post-osimertinib tumor samples was performed.
Results
Median age was 62 years (37–89), 64% were females, 86% had a PS ≤ 1, 54%/13% were never/current smokers. Median follow-up was 15.3 (IQR: 8.6–21.6) months. Overall response rate was 80%, median progression-free survival 12.1 months (95% CI 8.3–18.3), median overall survival 28 months (95% CI 20.2-not reached [NR]) and median treatment duration 18.8 months (95%CI 16-8-NR). PD occurred in 36 patients (72%). 73% had oligo-PD. Median osimertinib treatment duration in patients with oligo-PD was 19.6 vs. 7 months if systemic PD (p = 0.007). The number of progressive lesions in patients with oligo-PD was 1 (27%), 2 (35%) and 3–5 (39%). Sites of PD included lungs (56%), bones (44%), and brain (17%). Sixteen patients with oligo-PD continued treatment with osimertinib for a median of 6.7 months beyond PD. Thirteen received local ablative treatment (LAT). In pre- and post-PD tumor tissue multiple molecular alterations were detected.
Conclusion
In patients with acquired resistance to osimertinib, we observed a high rate (73%) of oligo-PD. Outcomes of patients receiving LAT were favorable, supporting the concept of osimertinib treatment beyond progression in combination with LAT of progressing lesions.
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