Resistance to Oral Therapy in Lung Cancer (RESTKI)

Mechanisms of Resistance to 3rd Generation Thyrosine Kinase Inhibitors in Lung Cancer

In the management of non-small cell lung cancer of the adenocarcinoma type, different therapeutic strategies can be proposed. These strategies are defined according to the results of a biological analysis of blood and/or tissue samples from the lung tumor. Mutations in the tumor DNA are sought. Thus, patients with sensitizing mutations can benefit from a treatment with a 3rd generation tyroine kinase inhibitor (TKI) whose efficacy has been widely demonstrated. Patients without tumor mutations will not benefit. However, resistance to TKIs appears after a certain time, often linked to the appearance of new mutations in the tumor. For this reason, blood biologic analyses are regularly performed to search for the emergence of resistance mutations and to propose a therapeutic alternative as soon as possible.

These analyses are performed routinely in the laboratory. In the course of these analyses, the investigators have identified conventional mutations but also new mutations not previously described in the literature.

Our objective is to list all the molecular abnormalities revealed during blood biological analyses, to determine their frequency and to study whether certain abnormalities can be linked to resistance to TKI.

Study Overview

• Status: Completed
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Other: Description of the molecular alterations detected in blood samples of patients treated by osimertinib

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• France
  • Hérault
    • Montpellier, Hérault, France, 34000
      • University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with metastatic adenocarcinoma

Description

Inclusion Criteria:

• advanced non-small cell lung cancer stage IIIB/IV
• Documentation of activating EGFR mutations (exon 19 deletions or exon 21 L858R substitution mutations) at the time of initial diagnosis
• Patient may receive up to one line of third EGFR TKI
• Plasma sample testing performed to detect EGFR TKI resistance

Exclusion Criteria:

• Patients have other concurrent cancers
• Patients who are not eligible receive TKI

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Osimertinib treated patients; Patients with metastatic adenocarcinoma of the lung for whom a 3rd generation TKI therapy is proposed and a search for resistance mutation by blood analysis as part of the usual management.

Other: Description of the molecular alterations detected in blood samples of patients treated by osimertinib; Description of the molecular alterations detected in blood samples of patients treated by osimertinib. This test is usualyy performed routinely to detect conventional mutations including EGFR T790M. We performed panel of genes screeining based on next generation sequencing. Thius, iIn some cases, new mutations can be detected by this assay.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Description of the molecular alterations detected in patients treated with 3rd TKI and assessment link with progression free survival and overall survival features.	This retrospective study will collate the molecular alterations detected during routine analysis. The elements extracted from the file will be age, sex, type of tumor and clinical-histological characteristics, dates of diagnosis and start of treatment. In addition, information on the dates of appearance of resistances (radiographic or clinical) will also be provided. No additional analysis will be performed since the study will consist of the analysis of data generated by the analyses performed in the context of patient management and biological monitoring. This research does not aim to modify your care. There will be no additional consultation or examination, nor will there be any changes in the treatment prescribed by your doctor.	The analysis of the TKI effectiveness and the appearance of mutations will be performed over a period of 24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of detected molecular alterations	Frequency of detected molecular alterations	The analysis of the TKI effectiveness and the appearance of mutations will be performed over a period of 24 months.

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Study Director: Jerome Solassol, UH Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Actual): July 1, 2020
• Study Completion (Actual): November 28, 2020

Study Registration Dates

• First Submitted: September 4, 2020
• First Submitted That Met QC Criteria: September 11, 2020
• First Posted (Actual): September 14, 2020

Study Record Updates

• Last Update Posted (Actual): December 29, 2020
• Last Update Submitted That Met QC Criteria: December 28, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Mutations; 3rd Tyrosine kinase inhibitor; Cell free DNA
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Osimertinib
• Other Study ID Numbers: RECHMPL20_0519

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No