Real-world Analysis of Workup at Disease Progression and Implementation of Osimertinib for EGFR+ NSCLC

Tyrosine kinase inhibitors (TKI) have greatly improved prognosis of epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC), with tumor responses in the majority of cases and a median overall survival currently exceeding 2.5 years. However, clinical courses vary widely and eventual treatment failure is inevitable. The most common resistance mechanism against first- and second-generation EGFR inhibitors is the EGFR T790M mutation, which emerges in about 50% of cases and is amenable to next-line treatment with the third-generation compound osimertinib. However, experience in everyday clinical practice shows that implementation of EGFR TKI sequencing is often problematic, for example because a considerable number of EGFR+ NSCLC patients failing first- and second-generation EGFR inhibitors do not undergo T790M mutation testing at the time of disease progression. This study will use patient records to analyze the clinical course of EGFR+ NSCLC patients treated with first- and second-generation EGFR inhibitors at the Thoraxklinik Heidelberg (Germany) during the past years. The main aim is to analyze the diagnostic and therapeutic measures, including implementation of osimertinib, taken at the time of disease progression as well as their effect on patient outcome in a real-world, routine clinical setting.

Study Overview

• Status: Completed
• Conditions: EGFR Positive Non-small Cell Lung Cancer

• Study Type: Observational
• Enrollment (Actual): 400

Contacts and Locations

Study Locations

• Germany
  • Heidelberg, Germany, 69126
    • Thoraxklinik-Heidelberg gGmbH - Universitätsklinikum Heidelberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All NSCLC patients with activating EGFR mutations treated with EGFR TKI at the Thoraxklinik Heidelberg between 2010 and 2019.

Description

Inclusion Criteria:

• histologically confirmed locally advanced (stage III) and not suitable for definitive local treatment, or metastatic (stage IV) NSCLC
• activating EGFR mutation confirmed
• treatment with EGFR TKI

Exclusion Criteria:

none

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
TKI-treated advanced EGFR+ NSCLC; Patients with advanced EGFR-mutated non-small cell lung cancer treated with tyrosine kinase inhibitors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fraction of EGFR+ NSCLC patients with sequential TKI treatment	the rate of rebiopsy and molecular workup (especially T790M testing) at disease progression under treatment with first-/second-generation EGFR inhibitors; the frequency of T790M mutations in the molecular workup of patients with disease progression under first-/second-generation EGFR inhibitors; the actual rate of osimertinib implementation after failure of first-/second-generation EGFR inhibitors in the "real-world" setting.	assessment will performed retrospectively for all study patients from September 2019 until June 2020

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-free survival (PFS) of patients treated with first-/second-generation EGFR inhibitors and/or osimertinib in the real-world setting	assessment will performed retrospectively for all study patients from September 2019 until June 2020
Time-to-next-treatment (TNT)	Time-to-next-treatment (TNT) of patients treated with first-/second-generation EGFR inhibitors and/or osimertinib in the real-world setting	assessment will performed retrospectively for all study patients from September 2019 until June 2020
Time-to-chemotherapy (TTC)	Time-to-chemotherapy (TTC) of patients treated with first-/second-generation EGFR inhibitors and/or osimertinib in the real-world setting	assessment will performed retrospectively for all study patients from September 2019 until June 2020
Overall survival (OS)	Overall survival (OS) of patients treated with first-/second-generation EGFR inhibitors and/or osimertinib in the real-world setting	assessment will performed retrospectively for all study patients from September 2019 until June 2020

Collaborators and Investigators

• Sponsor: Thoraxklinik-Heidelberg gGmbH
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Petros Christopoulos, MD, Thoraxklinik-Heidelberg gGmbH - Universitätsklinikum Heidelberg

Publications and helpful links

General Publications

• Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010 Jun 24;362(25):2380-8. doi: 10.1056/NEJMoa0909530.
• Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. doi: 10.1056/NEJMoa1612674. Epub 2016 Dec 6.
• Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Munoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group in collaboration with Groupe Francais de Pneumo-Cancerologie and Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. doi: 10.1016/S1470-2045(11)70393-X. Epub 2012 Jan 26.
• Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. doi: 10.1200/JCO.2012.44.2806. Epub 2013 Jul 1.
• Schrank Z, Chhabra G, Lin L, Iderzorig T, Osude C, Khan N, Kuckovic A, Singh S, Miller RJ, Puri N. Current Molecular-Targeted Therapies in NSCLC and Their Mechanism of Resistance. Cancers (Basel). 2018 Jul 4;10(7):224. doi: 10.3390/cancers10070224.

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2019
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: September 19, 2019
• First Submitted That Met QC Criteria: September 25, 2019
• First Posted (Actual): September 26, 2019

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Osimertinib; EGFR T790M; Tyrosine Kinase Inhibitor; EGFR mutation; Non-small cell lung carcinoma
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Disease Progression
• Other Study ID Numbers: S-469/19; ESR-19-14460 (Other Identifier: AstraZeneca)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No