Trial Outcomes & Findings for Afatinib as Second-line Therapy for Lung Cancer With Epidermal Growth Factor Receptor (EGFR) Mutation (NCT NCT02208843)
NCT ID: NCT02208843
Last Updated: 2018-12-17
Results Overview
As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
60 participants
Primary outcome timeframe
Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days
Results posted on
2018-12-17
Participant Flow
An open-label, single-arm phase IV study to assess the efficacy and safety of Afatinib as second-line therapy for patients with locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) harbouring an Epidermal Growth Factor Receptor(EGFR) mutation (Del19 or L858R) who have failed first-line treatment with platinum-based chemotherapy.
All patients were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that all subjects met all inclusion/exclusion criteria. Subjects were not to be entered to trial treatment if any one of the specific entry criteria were not met.
Participant milestones
| Measure |
Afatinib 40 mg
All patients received continuous daily treatment with Afatinib at a starting dose of 40 milligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food.
|
|---|---|
|
Overall Study
STARTED
|
60
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
60
|
Reasons for withdrawal
| Measure |
Afatinib 40 mg
All patients received continuous daily treatment with Afatinib at a starting dose of 40 milligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food.
|
|---|---|
|
Overall Study
Clinical symptoms of progression
|
2
|
|
Overall Study
Progression disease according to RECIST
|
24
|
|
Overall Study
Adverse Event
|
12
|
|
Overall Study
Protocol Violation
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Switched to commercial afatinib
|
20
|
Baseline Characteristics
Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.
Baseline characteristics by cohort
| Measure |
Afatinib 40 mg
n=60 Participants
All patients received continuous daily treatment with Afatinib at a starting dose of 40 milligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food.
|
|---|---|
|
Age, Continuous
|
59.9 Years
STANDARD_DEVIATION 9.8 • n=5 Participants • Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.
|
|
Sex: Female, Male
Female
|
33 Participants
n=5 Participants • Treated Set (TS): The TS included all patients who were documented to have taken at least 1 dose of afatinib.
|
|
Sex: Female, Male
Male
|
27 Participants
n=5 Participants • Treated Set (TS): The TS included all patients who were documented to have taken at least 1 dose of afatinib.
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants • Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.
|
|
Race (NIH/OMB)
Asian
|
19 Participants
n=5 Participants • Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants • Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants • Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.
|
|
Race (NIH/OMB)
White
|
41 Participants
n=5 Participants • Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants • Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants • Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.
|
PRIMARY outcome
Timeframe: Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 daysPopulation: Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.
As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions
Outcome measures
| Measure |
Afatinib 40 mg
n=60 Participants
All patients received continuous daily treatment with Afatinib at a starting dose of 40 milligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food.
|
|---|---|
|
Objective Tumour Response (Complete Response [CR], Partial Response [PR]) as Assessed by the Investigator According to the RECIST Version 1.1
|
50 Percentage of participants
Interval 36.8 to 63.2
|
SECONDARY outcome
Timeframe: Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 daysPopulation: Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.
Progression-free survival (PFS) is the time from treatment start to disease progression (or death if the patient died before progression). PFS as assessed based on investigator review according to the response evaluation criteria in solid tumours (RECIST) version 1.1.
Outcome measures
| Measure |
Afatinib 40 mg
n=60 Participants
All patients received continuous daily treatment with Afatinib at a starting dose of 40 milligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food.
|
|---|---|
|
Progression-free Survival (PFS) as Assessed by the Investigator According to RECIST 1.1.
|
10.94 Months
Interval 6.44 to 13.2
|
SECONDARY outcome
Timeframe: Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 daysPopulation: Treated Set (TS): The TS includes all patients who were documented to have taken at least 1 dose of afatinib.
As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Outcome measures
| Measure |
Afatinib 40 mg
n=60 Participants
All patients received continuous daily treatment with Afatinib at a starting dose of 40 milligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food.
|
|---|---|
|
Disease Control (CR, PR, Stable Disease [SD]) as Assessed by the Investigator According to RECIST 1.1
|
83.3 Percentage of participants
Interval 71.5 to 91.7
|
Adverse Events
Afatinib 40 mg
Serious events: 21 serious events
Other events: 56 other events
Deaths: 11 deaths
Serious adverse events
| Measure |
Afatinib 40 mg
n=60 participants at risk
All patients received continuous daily treatment with Afatinib at a starting dose of 40 milligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food.
|
|---|---|
|
Cardiac disorders
Cardiac arrest
|
1.7%
1/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Gastrointestinal disorders
Diarrhoea
|
6.7%
4/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Infections and infestations
Pneumonia
|
3.3%
2/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Investigations
Blood creatinine increased
|
1.7%
1/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
1.7%
1/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion
|
1.7%
1/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Nervous system disorders
Brain oedema
|
3.3%
2/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Nervous system disorders
Epilepsy
|
1.7%
1/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Nervous system disorders
Hemiparesis
|
1.7%
1/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Nervous system disorders
Nervous system disorder
|
1.7%
1/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Nervous system disorders
Neurological decompensation
|
1.7%
1/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Nervous system disorders
Seizure
|
3.3%
2/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Renal and urinary disorders
Acute kidney injury
|
3.3%
2/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
1.7%
1/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Vascular disorders
Deep vein thrombosis
|
1.7%
1/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
General disorders
Disease progression
|
1.7%
1/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
General disorders
Fatigue
|
1.7%
1/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
Other adverse events
| Measure |
Afatinib 40 mg
n=60 participants at risk
All patients received continuous daily treatment with Afatinib at a starting dose of 40 milligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
20.0%
12/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Blood and lymphatic system disorders
Leukopenia
|
6.7%
4/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.3%
5/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Gastrointestinal disorders
Diarrhoea
|
73.3%
44/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Gastrointestinal disorders
Nausea
|
20.0%
12/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Gastrointestinal disorders
Stomatitis
|
8.3%
5/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
6/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Infections and infestations
Paronychia
|
23.3%
14/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Investigations
Gamma-glutamyltransferase increased
|
8.3%
5/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Investigations
Weight decreased
|
8.3%
5/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Metabolism and nutrition disorders
Decreased appetite
|
8.3%
5/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
6.7%
4/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
6.7%
4/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
21.7%
13/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
6.7%
4/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
8.3%
5/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.7%
4/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Nervous system disorders
Dizziness
|
6.7%
4/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.7%
4/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Skin and subcutaneous tissue disorders
Acne
|
6.7%
4/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
10.0%
6/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
15.0%
9/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
8.3%
5/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Skin and subcutaneous tissue disorders
Nail pitting
|
6.7%
4/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.3%
5/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
30.0%
18/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
General disorders
Fatigue
|
15.0%
9/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
|
General disorders
Mucosal inflammation
|
20.0%
12/60 • From first drug administration until 28 days after last drug administration, up to 830 days
|
Additional Information
Boehringer Ingelheim, Call Centre
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER