Abstract 2853
Background
Osimertinib is the preferable therapeutic option for many epidermal growth factor receptor (EGFR)+ non-small cell lung cancer (NSCLC) patients failing other tyrosine kinase inhibitors (TKI), but implementation of EGFR TKI sequencing is often problematic.
Methods
We retrospectively studied the clinical course of EGFR+ NSCLC patients that received first-/second-generation TKI at our institutions and had their last follow-up after osimertinib approval (02/2016).
Results
A total of n = 283 EGFR+ NSCLC patients received erlotinib (45%), gefitinib (19%) and/or afatinib (36%) in the 1st-4th treatment lines with a median age of 66 years, a median ECOG performance status of 0 (137/266 patients with available data) and a predominance of female (183/283=65%) never-/light-smokers (177/283=63%). Median overall survival (OS) from treatment start was 32.7 months (95% confidence interval [CI] 28.1 – 37.3) with 2.2 treatment lines on average (standard deviation 1.4). EGFR T790M testing was performed for 139/203 (68%) patients after TKI failure, with a positive result in 77/139 (55%) and subsequent treatment with osimertinib in 50/77 (65%). Overall, 50/203 (25%) of patients received osimertinib, with a median OS of 44.9 (27.9 – 62.1) months, significantly longer than the 30.4 (20.6 – 40.3) months for patients with alternative or no subsequent therapies (logrank p = 0.053, Breslow p = 0.002). Among the 134 deceased patients with complete follow-up, 84 (63%) received additional systemic treatment (37% chemotherapy, 16% osimertinib, 8% only alternative EGFR inhibitors, 2% only immunotherapy), while 50/134 (37%) died without next-line therapy. For patients that subsequently received chemotherapy, median time to start of chemotherapy was 11.6 (8.9 – 14.3) months.
Conclusions
Sequential treatment with osimertinib after first- or second-generation EGFR inhibitors significantly prolongs OS, but in the real-world setting a considerable fraction of patients will not be able to benefit from that. Main obstacles in our cohort were lack of EGFR T790M testing (32% of total cases), T790M-negative progression (45% of tested cases), and rapid clinical deterioration without the chance of next-line therapy (about one-third of patients).
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Thoraxklinik at Heidelberg University Hospital.
Funding
Thoraxklinik at Heidelberg University Hospital AstraZeneca.
Disclosure
P. Christopoulos: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: Chugai; Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Boehringer; Research grant / Funding (institution): Takeda. F. Bozorgmehr: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self): MSD. J.B. Kuon: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Cellgene. V. Endris: Honoraria (self), Advisory / Consultancy: ThermoFisher; Honoraria (self), Advisory / Consultancy: AstraZeneca. T. Bochtler: Honoraria (institution), Research grant / Funding (institution): Roche. F.J.F. Herth: Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Boehringer; Honoraria (self), Research grant / Funding (institution): Chiesi; Honoraria (self), Research grant / Funding (institution): Teva; Honoraria (self): Pulmonx BTG; Honoraria (self): Olympus. C. Heussel: Honoraria (self), Honoraria (institution): Novartis, Basilea, Bayer, Grifols, Boehringer, Pierre Fabre, Covidien, Siemens, Chiesi, Intermune, MEDA Pharma, Bracco, Pfizer, MSD, Roche, Lilly, AstraZeneca, Schering-Plough, Essex, Gilead, MeVis, Fresenius, Astellas; Shareholder / Stockholder / Stock options: GSK. T. Muley: Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Roche. J.R. Fischer: Advisory / Consultancy: Boehringer, Roche, Celgene and AstraZeneca. A. Stenzinger: Honoraria (self), Advisory / Consultancy: Novartis, AstraZeneca, ThermoFisher, BMS; Honoraria (self): BMS, Illumina, AstraZeneca, Novartis, ThermoFisher, MSD, Roche; Research grant / Funding (institution): Chugai; Honoraria (self): Illumina, AstraZeneca, Novartis, ThermoFisher . M. Thomas: Honoraria (self), Advisory / Consultancy: Novartis, Lilly, BMS, MSD, Roche, Celgene, Takeda, AbbVie, Boehringer, Lilly, MSD, Takeda; Research grant / Funding (institution): AstraZeneca, BMS, Celgene, Novartis, Roche, Takeda. All other authors have declared no conflicts of interest.
Resources from the same session
2023 - Patients with brain metastases treated with afatinib in clinical practice – results from the prospective non-interventional study GIDEON
Presenter: Eckart Laack
Session: Poster Display session 1
Resources:
Abstract
1613 - Lerociclib (G1T38), an oral CDK4/6 inhibitor, dosed continuously in combination with osimertinib for EGFRmut non-small cell lung cancer: initial Phase 1b results
Presenter: David Berz
Session: Poster Display session 1
Resources:
Abstract
1974 - A Phase II Open-Label, Multicentre Study to Assess the Anti-tumour Activity of Afatinib in Patients with Activating Epidermal Growth Factor Receptor mutation (EGFRm) from Circulating Tumor DNA (CtDNA)
Presenter: Young-Chul Kim
Session: Poster Display session 1
Resources:
Abstract
3370 - Influence of cow’s milk on the absorption and exposure of erlotinib in NSCLC patients
Presenter: Geerten Veerman
Session: Poster Display session 1
Resources:
Abstract
5900 - PTEN loss as Predictor of Tumor Heterogeneity (TH) and Poor Prognosis in EGFR-mutant Advanced Non-Small Cell Lung Cancer (ANSCLC) Patients (pts) Receiving Tyrosine-Kinase Inhibitors (TKIs).
Presenter: Miriam Ferrara
Session: Poster Display session 1
Resources:
Abstract
1302 - Safety of lorlatinib in subgroups of patients from a phase 1/2 trial
Presenter: Enriqueta Felip
Session: Poster Display session 1
Resources:
Abstract
1497 - Brigatinib (BRG) in Asian vs non-Asian patients (pts) with crizotinib (CRZ)-refractory ALK+ NSCLC in the phase 2 ALTA trial
Presenter: Dae Ho Lee
Session: Poster Display session 1
Resources:
Abstract
2349 - The safety assessment of crizotinib and alectinib from real world data of 840 ALK-inhibitor naïve patients with NSCLC harboring ALK-rearrangement (WJOG9516L).
Presenter: Kei Kunimasa
Session: Poster Display session 1
Resources:
Abstract
1120 - Brigatinib in ALK TKI-pretreated ALK+ metastatic non-small cell lung cancer (mNSCLC): the Use Via Expanded Access to Brigatinib (UVEA-Brig) study
Presenter: Silvia Novello
Session: Poster Display session 1
Resources:
Abstract
5239 - Treatment patterns and outcomes for patients (pts) with anaplastic lymphoma kinase-positive (ALK+) advanced non-small-cell lung cancer (NSCLC) in US clinical practice
Presenter: Matthew Krebs
Session: Poster Display session 1
Resources:
Abstract