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

EGFR Positive Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04105153
• Other study ID #: S-469/19
• Secondary ID: ESR-19-14460
• Status: Completed
• Start date: April 15, 2019
• Est. completion date: December 1, 2019

Study information

• Verified date: November 2023
• Source: Thoraxklinik-Heidelberg gGmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 400
• Est. completion date: December 1, 2019
• Est. primary completion date: December 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Disease Progression
• EGFR Positive Non-small Cell Lung Cancer

Locations

Country	Name	City	State
Germany	Thoraxklinik-Heidelberg gGmbH - Universitätsklinikum Heidelberg	Heidelberg

Sponsors (2)

Lead Sponsor	Collaborator
Thoraxklinik-Heidelberg gGmbH	AstraZeneca

Country where clinical trial is conducted

Germany, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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