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Poster Display session 1

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

Date

28 Sep 2019

Session

Poster Display session 1

Topics

Tumour Site

Non-Small Cell Lung Cancer

Presenters

Petros Christopoulos

Citation

Annals of Oncology (2019) 30 (suppl_5): v602-v660. 10.1093/annonc/mdz260

Authors

P. Christopoulos1, A. Volckmar2, F. Bozorgmehr3, N. Magios4, J.B. Kuon4, M. Kirchner2, D. Kazdal2, V. Endris2, T. Bochtler2, F.J.F. Herth5, C. Heussel1, H. Winter1, T. Muley1, M. Meister1, J.R. Fischer6, S. Rieken7, M. Faehling8, H. Bischoff9, A. Stenzinger10, M. Thomas9

Author affiliations

  • 1 Oncology, Thoraxklinik Heidelberg, 69126 - Heidelberg/DE
  • 2 Center For Molecular Pathology, Institute of Pathology, 69126 - Heidelberg/DE
  • 3 Department Of Thoracic Oncology, Thoraxklinik Heidelberg, 69126 - Heidelberg/DE
  • 4 Thoracic Oncology, Thoraxklinik Heidelberg, 69126 - Heidelberg/DE
  • 5 Pneumology, Thoraxklinik Heidelberg, 69126 - Heidelberg/DE
  • 6 Med Klinik Ii Onkologie, Klinik Loewenstein GmbH Med Klinik II Onkologie, 74245 - Löwenstein/DE
  • 7 Radiation Oncology, Department of Radiation Oncology, 69120 - Heidelberg/DE
  • 8 Klinik Für Kardiologie Und Pneumologie, Klinikum Esslingen, 73730 - Esslingen/DE
  • 9 Medical Oncology, Thoraxklinik Heidelberg, 69126 - Heidelberg/DE
  • 10 Institute Of Pathology, University Hospital Heidelberg, Institute of Pathology, 69120 - Heidelberg/DE

Resources

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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.

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