2853 - Real-world implementation of sequential targeted therapies for EGFR-mutated NSCLC

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 1^st-4^th 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.