Afatinib Osimertinib Sequencing NIS

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03370770
• Collaborator: (none)
• Enrollment: 204
• Location: 1
• Actual Duration (Months): 23
• Patients Per Site Per Month: 8.9

Study Details

Study Description

Brief Summary

This is a non-interventional, multi-country, multi-centre cohort study based on existing data from medical records of patients with EGFR mutation-positive advanced NSCLC treated with afatinib (Gi(l)otrif®) as the first-line treatment followed by osimertinib in case the T790M resistance mutation was developed.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: Afatinib; Drug: Osimertinib

Study Design

• Study Type: Observational
• Actual Enrollment: 204 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: GioTag: Real-world Data Study on Sequential Therapy With Gi(l)Otrif®/ Afatinib as First-line Treatment Followed by Osimertinib in Patients With EGFR Mutation Positive Advanced Non-small Cell Lung Cancer
• Actual Study Start Date: Dec 28, 2017
• Actual Primary Completion Date: Nov 28, 2019
• Actual Study Completion Date: Nov 28, 2019

Arms and Interventions

Arm	Intervention/Treatment
patients with EGFR mutation-positive NSCLC (Non-Small Cell Lung Cancer) (Epidermal Growth Factor Receptor)	Drug: Afatinib; GILOTRIF, GIOTRIF, XOVOLTIB; Drug: Osimertinib; on T790M resistance mutation was developed

Outcome Measures

Primary Outcome Measures

1. Time on Treatment With Afatinib (Gi(l)Otrif®) Followed by Osimertinib [Data collected from start of treatment until data entry completion, up to 96.8 months for first analysis and up to 114.1 months for the extension analysis.]

   Time on treatment, which was defined as time in months from the start date of Afatinib (Gi[l]otrif®) treatment ('start date of initial dose' for First-Line Treatment) to the end date of Osimertinib treatment (maximum between 'end date of initial dose' and the last 'end date of dose modification' for Second-Line Treatment) or death date due to any cause ('date of death'). Time on treatment (months) = Time on treatment (days)/30.4375. 'Time on treatment was analysed using Kaplan-Meier method, and the median along with two-sided 90% confidence interval was displayed using the Greenwood's formula for estimation of standard errors.

Secondary Outcome Measures

1. The Percentage of Participants With Different Types of Mutations After Categorisation [Data collected from start of treatment until data entry completion; up to 96.8 months.]

   Different types of resistance mutations identified at the time of discontinuation of osimertinib treatment were systematically reviewed and categorised.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC)

• The tumour harbours common EGFR mutations (Del19, L858R) at start of first-line treatment

• Patients who initiated second-line osimertinib treatment for acquired T790M mutation at least 10 months prior to data entry, AND who were treated with afatinib (Gi(l)otrif®) in the first-line

• Patients treated with osimertinib within an EAP/CUP or regular clinical practice

• Age ≥ 18 years

• Signed and dated written informed consent per regulations (Exemption of a written informed consent for NIS based on existing data in countries per local regulations and legal requirements)

Exclusion Criteria:

• Patients who received drug(s) other than osimertinib as the second-line treatment and/or patients who received drug(s) other than afatinib (Gi(l)otrif®) as the first-line treatment

• Patients with active brain metastases at start of treatment (either afatinib/Gi(l)otrif® or osimertinib)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Otto-Wagner Hospital	Vienna		Austria	1140

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

• Statistical Analysis Plan - Mar 11, 2020
• Study Protocol - Mar 6, 2019

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT03370770
• Other Study ID Numbers: 1200-0286
• First Posted: Dec 12, 2017
• Last Update Posted: Dec 24, 2020
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma, Non-Small-Cell Lung; Osimertinib; Afatinib

Study Results

Participant Flow

Recruitment Details

Non-interventional, multi-centre cohort study based on existing data from medical records of patients with epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC) treated with afatinib (Gi[l]otrif®) as first-line treatment followed by osimertinib in case the T790M resistance mutation was developed. The study included an extension analysis using additional collected data of the enrolled patients.

Pre-assignment Detail

All patients were screened for eligibility to participate in the trial. Only patients that met all the inclusion and none of the exclusion criteria were included in the trial.

Arm/Group Title	Patients With EGFR Mutation-positive NSCLC
Arm/Group Description	Patients with EGFR mutation-positive NSCLC with acquired T790M mutation at least 10 months prior to data entry, and who were treated with afatinib (Gi[l]otrif®) (50mg or 40mg or 30mg or 20mg tablet once daily as indicated in the approved labels of afatinib (Gi[l]otrif®)) in the first-line line treatment followed by second-line osimertinib treatment (80 milligram (mg) or 40 mg tablets once daily as indicated in the approved labels of osimertinib).
Period Title: Overall Study
STARTED	204
COMPLETED	98
NOT COMPLETED	106

Baseline Characteristics

Arm/Group Title	Patients With EGFR Mutation-positive NSCLC
Arm/Group Description	Patients with EGFR mutation-positive NSCLC with acquired T790M mutation at least 10 months prior to data entry, and who were treated with afatinib (Gi[l]otrif®) (50mg or 40mg or 30mg or 20mg tablet once daily as indicated in the approved labels of afatinib (Gi[l]otrif®)) in the first-line line treatment followed by second-line osimertinib treatment (80 milligram (mg) or 40 mg tablets once daily as indicated in the approved labels of osimertinib).
Overall Participants	204
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.1 (10.48)
Sex: Female, Male (Count of Participants)
Female	110 53.9%
Male	94 46.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	19 9.3%
Not Hispanic or Latino	181 88.7%
Unknown or Not Reported	4 2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 1%
Asian	50 24.5%
Native Hawaiian or Other Pacific Islander	1 0.5%
Black or African American	18 8.8%
White	120 58.8%
More than one race	0 0%
Unknown or Not Reported	13 6.4%

Outcome Measures

1. Primary Outcome

Title	Time on Treatment With Afatinib (Gi(l)Otrif®) Followed by Osimertinib
Description	Time on treatment, which was defined as time in months from the start date of Afatinib (Gi[l]otrif®) treatment ('start date of initial dose' for First-Line Treatment) to the end date of Osimertinib treatment (maximum between 'end date of initial dose' and the last 'end date of dose modification' for Second-Line Treatment) or death date due to any cause ('date of death'). Time on treatment (months) = Time on treatment (days)/30.4375. 'Time on treatment was analysed using Kaplan-Meier method, and the median along with two-sided 90% confidence interval was displayed using the Greenwood's formula for estimation of standard errors.
Time Frame	Data collected from start of treatment until data entry completion, up to 96.8 months for first analysis and up to 114.1 months for the extension analysis.

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): All patients who were enrolled into the study, met all inclusion criteria and did not meet any exclusion criteria and provided a written and signed informed consent. 1 Patient was excluded from extension analysis due to conflicting data on the discontinuation date of osimertinib treatment.

Arm/Group Title	Patients With EGFR Mutation-positive NSCLC
Arm/Group Description	Patients with EGFR mutation-positive NSCLC with acquired T790M mutation at least 10 months prior to data entry, and who were treated with afatinib (Gi[l]otrif®) (50mg or 40mg or 30mg or 20mg tablet once daily as indicated in the approved labels of afatinib (Gi[l]otrif®)) in the first-line line treatment followed by second-line osimertinib treatment (80 milligram (mg) or 40 mg tablets once daily as indicated in the approved labels of osimertinib).
Measure Participants	204
First analysis	27.6
Extension analysis	27.7

2. Secondary Outcome

Title	The Percentage of Participants With Different Types of Mutations After Categorisation
Description	Different types of resistance mutations identified at the time of discontinuation of osimertinib treatment were systematically reviewed and categorised.
Time Frame	Data collected from start of treatment until data entry completion; up to 96.8 months.

Outcome Measure Data

Analysis Population Description

Patients in the Full Analysis Set (FAS), who discontinued treatment and with positive test results (either EGFR sensitizing Mutation and/or T790M) available.

Arm/Group Title	Patients With EGFR Mutation-positive NSCLC
Arm/Group Description	Patients with EGFR mutation-positive NSCLC with acquired T790M mutation at least 10 months prior to data entry, and who were treated with afatinib (Gi[l]otrif®) (50mg or 40mg or 30mg or 20mg tablet once daily as indicated in the approved labels of afatinib (Gi[l]otrif®)) in the first-line line treatment followed by second-line osimertinib treatment (80 milligram (mg) or 40 mg tablets once daily as indicated in the approved labels of osimertinib).
Measure Participants	39
T790M positive	69.2 33.9%
Loss of T790M	20.5 10%
T790M positive, loss of sensitizing mutation	10.3 5%

Adverse Events

Time Frame	Adverse event information was not applicable for this study, as data were collected retrospectively. The approach was changed for the extension period: Adverse Events were collected from start of data collection once informed consent was signed onwards until the end of data collection, up to 18 months.
Adverse Event Reporting Description	Participants in the Full Analysis Set (FAS), who were included in the extension period.
Arm/Group Title	Patients With EGFR Mutation-positive NSCLC
Arm/Group Description	Patients with EGFR mutation-positive NSCLC with acquired T790M mutation at least 10 months prior to data entry, and who were treated with afatinib (Gi[l]otrif®) (50mg or 40mg or 30mg or 20mg tablet once daily as indicated in the approved labels of afatinib (Gi[l]otrif®)) in the first-line line treatment followed by second-line osimertinib treatment (80 milligram (mg) or 40 mg tablets once daily as indicated in the approved labels of osimertinib).
All Cause Mortality
	Patients With EGFR Mutation-positive NSCLC
	Affected / at Risk (%)	# Events
Total	31/203 (15.3%)
Serious Adverse Events
	Patients With EGFR Mutation-positive NSCLC
	Affected / at Risk (%)	# Events
Total	32/203 (15.8%)
Gastrointestinal disorders
Diarrhoea	1/203 (0.5%)
General disorders
Disease progression	27/203 (13.3%)
Death	1/203 (0.5%)
Infections and infestations
Sepsis	1/203 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer	1/203 (0.5%)
Skin and subcutaneous tissue disorders
Rash	1/203 (0.5%)
Other (Not Including Serious) Adverse Events
	Patients With EGFR Mutation-positive NSCLC
	Affected / at Risk (%)	# Events
Total	62/203 (30.5%)
Gastrointestinal disorders
Diarrhoea	52/203 (25.6%)
Stomatitis	21/203 (10.3%)
Infections and infestations
Paronychia	25/203 (12.3%)
Skin and subcutaneous tissue disorders
Rash	34/203 (16.7%)
Dermatitis	12/203 (5.9%)

Limitations/Caveats

This study has no comparator group limiting the interpretability of the results as they cannot be put into perspective.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.