Efficacy, Safety, Tolerability of Gefitinib as 1st Line in Caucasian Patients With EGFR Mutation Positive Advanced NSCLC

Conditions

Caucasian Patients With EGFR Mutation Positive Advanced NSCLC

Keywords

Gefitinib, EGFR TKI, efficacy, Caucasian patients, EGFR mutation positive advanced NSCLC, safety

Brief summary

This study is carried out to see how Caucasian patients with lung cancer which has EGFR mutation will respond to gefitinib (IRESSA™) as a first line treatment. Safety data will also be collected and analysed to confirm that treatment with gefitinib is safe and well tolerated.

Detailed description

An Open Label, Multicentre, Single Arm Study to Characterise the Efficacy, Safety and Tolerability of Gefitinib 250 mg (IRESSA™) as First line Treatment in Caucasian Patients, who have Epidermal Growth Factor Receptor (EGFR) Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer

James Dunyak, Jacqueline Buros‐Novik, Eric Novik, Hong Yan, Nidal Al‐Huniti

Bioinformatics, Convergence Science, and Systems Biology2019-07-01

10.1158/1538-7445.sabcs18-1674

Abstract 1674: Prediction of survival based on tumor size dynamics and new lesions in EGFR mutation-positive non-small cell lung cancer patients treated with gefitinib or carboplatin and paclitaxel

James Dunyak, Jacqueline Buros‐Novik, Eric Novik, Hong Yan, Nidal Al‐Huniti

Cancer Research2019-07-01

10.1158/1538-7445.am2019-1674

A joint model of tumor size dynamics and survival with new lesions in EGFR mutation-positive non-small cell lung cancer patients with treatment of gefitinib or carboplatin and paclitaxel.

James Dunyak, Hong Yan, Nidal Al‐Huniti

Journal of Clinical Oncology2019-05-201 citations

10.1200/jco.2019.37.15_suppl.e20697

Abstract 4761: Joint model of longitudinal tumor size and overall survival (OS) in non-small cell lung cancer (NSCLC): A Bayesian approach

Nidal Al‐Huniti, Hongmei Xu, Diansong Zhou, Helena Edlund, Sergey Aksenov et al. (7 authors)

Cancer Research2018-07-011 citations

10.1158/1538-7445.am2018-4761

Flipped script for gefitinib: A reapproved tyrosine kinase inhibitor for first-line treatment of epidermal growth factor receptor mutation positive metastatic nonsmall cell lung cancer

Brian S Bogdanowicz, Matthew A Hoch, Megan E. Hartranft

Journal of Oncology Pharmacy Practice2016-02-2514 citations

10.1177/1078155216634179

Gefitinib treatment in EGFR mutated caucasian NSCLC: circulating-free tumor DNA as a surrogate for determination of EGFR status.

Douillard JY, Ostoros G, Cobo M, Ciuleanu T, Cole R, McWalter G, Walker J, Dearden S, Webster A, Milenkova T, McCormack R.

2014-09-01347 citations

10.1097/jto.0000000000000263

First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study.

Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, Milenkova T.

2013-11-21300 citations

10.1038/bjc.2013.721

Interventions

DRUGGefitinib

250mg tablet oral, once daily until objective disease progression is documented or until other discontinuation criterion is met

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 130 Years

Healthy volunteers

No

Inclusion criteria

* Locally advanced or metastatic non-small cell lung cancer (i.e. cancer that has spread from where it started) which is EGFR mutation positive * Caucasian female or male patients aged 18 years or over * Measurable disease, i.e. at least one lesion, not previously irradiated, as ≥ 10 mm in the longest diameter (≥ 15 mm in short axis for lymph node )

Exclusion criteria

* Prior adjuvant chemotherapy or other systemic anti-cancer treatment less than 6 month, or palliative radiotherapy less than 4 weeks prior to start of study treatment. * Brain metastases or spinal cord compression, unless treated and stable without steroids * Any clinically significant illness, which will jeopardize the patients' safety and their participation in the study.

Design outcomes

Primary

Measure	Time frame	Description
Objective Response Rate (ORR) (Investigator)	Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months	% of patients in the Full analysis set who have a complete response \[CR\] or partial response \[PR\] confirmed by repeat imaging at least 4 weeks later with no evidence of progression between confirmation visits (as defined by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1)). CR: disappearance of all target lesions (TLs) & non-target lesions (NTLs). PR: \>= 30% decrease in the sum of diameters compared to baseline (with no evidence of progression) and the NTLs are at least stable with no evidence of new lesions. Outcome is based on measurements made at site by investigator.

Secondary

Measure	Time frame	Description
Disease Control Rate (DCR) (Investigator)	Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months	DCR is calculated as the % of the FAS patient population with a best visit response of CR, PR (a visit response of CR or PR which is confirmed at least 4 weeks later) or stable disease (SD). SD is defined as no evidence of CR, PR or progression and must have occurred at a minimum of 6 weeks after first dose of study treatment. (progression is defined as ≥20% increase in the sum of the diameters of target lesions from minimum; clinically significant progression in non-target lesions; the presence of a new lesion or death). Outcome is based on measurements made at site by investigator.
Progression - Free Survival (PFS) (Investigator)	Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months	PFS was defined as the time from the first dose of gefitinib study treatment until objective disease progression as defined by RECIST 1.1 (≥20% increase in the sum of the diameters of target lesions from minimum, clinically significant progression in non-target lesions or the presence of a new lesion) or death (by any cause in the absence of progression). Progression is based on measurements made at site by investigator.
Overall Survival (OS)	Survival follow up from first dose of gefitinib till death of the patient or till end of study in absence of death.	OS was defined as the time from first dose of gefitinib study treatment until death by any cause. Patients who had not died at the time of analysis were censored at the last date the patient was known to be alive.

Other

Measure	Time frame	Description
Objective Response Rate (ORR) (Independent Central Review))	Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months	% of patients in the Full analysis set who have a complete response \[CR\] or partial response \[PR\] confirmed by repeat imaging at least 4 weeks later with no evidence of progression between confirmation visits (as defined by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1)). CR: disappearance of all target lesions (TLs) & non-target lesions (NTLs). PR: \>= 30% decrease in the sum of diameters compared to baseline (with no evidence of progression) and the NTLs are at least stable with no evidence of new lesions. Outcome is based on measurements of scans by central review.
Progression - Free Survival (PFS) (Independent Central Review)	Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months	PFS was defined as the time from the first dose of gefitinib study treatment until objective disease progression as defined by RECIST 1.1 (≥20% increase in the sum of the diameters of target lesions from minimum, clinically significant progression in non-target lesions or the presence of a new lesion) or death (by any cause in the absence of progression). Progression is based on measurements of scans by central review.
Disease Control Rate (DCR) (Independent Central Review)	Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months	DCR is calculated as the % of the FAS patient population with a best visit response of CR, PR (a visit response of CR or PR which is confirmed at least 4 weeks later) or stable disease (SD). SD is defined as no evidence of CR, PR or progression and must have occurred at a minimum of 6 weeks after first dose of study treatment. (progression is defined as ≥20% increase in the sum of the diameters of target lesions from minimum; clinically significant progression in non-target lesions; the presence of a new lesion or death). Outcome is based on measurements of scans by central review.

Countries

Bulgaria, France, Greece, Hungary, Italy, Norway, Poland, Portugal, Romania, Spain, Switzerland, Turkey (Türkiye), United Kingdom

Participant flow

Recruitment details

1060 Caucasian patients with locally advanced or metastatic NSCLC were screened, and 118 patients had activating sensitizing EGFR mutation eligible for the study (EGFR M+). 106 EGFR M+ patients received at least 1 dose of gefitinib. One patient had EGFR mutation not eligible for the study (EGFR M+I) and was started on gefitinib in error.

Participants by arm

Arm	Count
Gefitinib Gefitinib 250 mg oral tablets once daily, administered continuously from Visit 2 until objective disease progression was documented or any other criterion for discontinuation was met. Gefitinib tablets were taken at approximately the same time each day.	106
Total	106

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	29
Overall Study	Due to EGFR M+I patient	1
Overall Study	Due to objective disease progression	1
Overall Study	Lost to Follow-up	2
Overall Study	Withdrawal by Subject	3

Baseline characteristics

Characteristic	Gefitinib
Age, Continuous	64.0 Years STANDARD_DEVIATION 11.81
Age, Customized > =18 to < 65 Years	52 Participants
Age, Customized > =65 to < 75 Years	28 Participants
Age, Customized > =75 Years	26 Participants
Gender Female	75 Participants
Gender Male	31 Participants
Race/Ethnicity, Customized Other	0 Participants
Race/Ethnicity, Customized White	106 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	87 / 107
serious Total, serious adverse events	21 / 107

Outcome results

Primary

Objective Response Rate (ORR) (Investigator)

% of patients in the Full analysis set who have a complete response \[CR\] or partial response \[PR\] confirmed by repeat imaging at least 4 weeks later with no evidence of progression between confirmation visits (as defined by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1)). CR: disappearance of all target lesions (TLs) & non-target lesions (NTLs). PR: \>= 30% decrease in the sum of diameters compared to baseline (with no evidence of progression) and the NTLs are at least stable with no evidence of new lesions. Outcome is based on measurements made at site by investigator.

Time frame: Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months