Header

UZH-Logo

Maintenance Infos

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


Schmid, S; Klingbiel, D; Aeppli, S; Britschgi, C; Gautschi, O; Pless, M; Rothschild, S; Wannesson, L; Janthur, W; Foerbs, D; Demmer, I; Jochum, W; Früh, M (2019). Patterns of progression on osimertinib in EGFR T790M positive NSCLC: A Swiss cohort study. Lung Cancer, 130:149-155.

Abstract

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.

Abstract

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.

Statistics

Citations

Dimensions.ai Metrics
16 citations in Web of Science®
16 citations in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology and Hematology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Oncology
Health Sciences > Pulmonary and Respiratory Medicine
Life Sciences > Cancer Research
Language:English
Date:April 2019
Deposited On:15 Oct 2019 15:50
Last Modified:29 Jul 2020 11:26
Publisher:Elsevier
ISSN:0169-5002
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.lungcan.2019.02.020
PubMed ID:30885336

Download

Full text not available from this repository.
View at publisher

Get full-text in a library