Trial Outcomes & Findings for Afatinib in NSCLC With HER2 Mutation (NCT NCT02369484)
NCT ID: NCT02369484
Last Updated: 2022-08-24
Results Overview
Disease control (DC) is defined as complete or partial response, or disease stabilisation lasting at least 12 weeks. Disease control will be determined using RECIST 1.1 criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. Progression (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum recorded on the trial. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions denotes disease progression. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters recorded on the trial.
COMPLETED
PHASE2
13 participants
at interim (after the first 9 pts have been followed for 12 weeks) & final analysis (approx. 40 months after inclusion of first pt)
2022-08-24
Participant Flow
ETOP/7-14 NICHE trial was activated in December 2014. The first patient was enrolled on September 2015 while the last one on August 2016, before accrual was suspended in October 2016. Patients were enrolled in 3 centers (Netherlands Cancer Institute of Amsterdam, Vall d' Herbon Univesity Hospital (Spain) and Universitatsklinikum Koln (Germany)).
All 13 patients eligible for enrollment received treatment
Participant milestones
| Measure |
Afatinib
Afatinib 40 mg p.o./day until tumour progression or lack of tolerability
|
|---|---|
|
Overall Study
STARTED
|
13
|
|
Overall Study
COMPLETED
|
13
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Afatinib
n=13 Participants
Afatinib 40 mg p.o./day until tumour progression or lack of tolerability
Afatinib: 40mg p.o./ day until documented progression or unacceptable toxicity
|
|---|---|
|
Age, Continuous
|
59 years
n=13 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=13 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=13 Participants
|
|
Region of Enrollment
Netherlands
|
7 participants
n=13 Participants
|
|
Region of Enrollment
Germany
|
3 participants
n=13 Participants
|
|
Region of Enrollment
Spain
|
3 participants
n=13 Participants
|
|
Smoking history
Current
|
1 Participants
n=13 Participants
|
|
Smoking history
Former
|
4 Participants
n=13 Participants
|
|
Smoking history
Never
|
8 Participants
n=13 Participants
|
|
ECOG Performance status
0
|
7 Participants
n=13 Participants
|
|
ECOG Performance status
1
|
4 Participants
n=13 Participants
|
|
ECOG Performance status
2
|
2 Participants
n=13 Participants
|
|
T parameter
T1b
|
1 Participants
n=13 Participants
|
|
T parameter
T2a
|
3 Participants
n=13 Participants
|
|
T parameter
T3
|
3 Participants
n=13 Participants
|
|
T parameter
T4
|
6 Participants
n=13 Participants
|
|
N parameter
N0
|
5 Participants
n=13 Participants
|
|
N parameter
N2
|
3 Participants
n=13 Participants
|
|
N parameter
N3
|
5 Participants
n=13 Participants
|
|
M parameter
M0
|
1 Participants
n=13 Participants
|
|
M parameter
M1a
|
6 Participants
n=13 Participants
|
|
M parameter
M1b
|
6 Participants
n=13 Participants
|
|
TNM staging
T1b-N3-M1b
|
1 Participants
n=13 Participants
|
|
TNM staging
T2a-N0-M1a
|
1 Participants
n=13 Participants
|
|
TNM staging
T2a-N2-M1b
|
1 Participants
n=13 Participants
|
|
TNM staging
T2a-N3-M1b
|
1 Participants
n=13 Participants
|
|
TNM staging
T3-N0-M1b
|
1 Participants
n=13 Participants
|
|
TNM staging
T3-N2-M1a
|
1 Participants
n=13 Participants
|
|
TNM staging
T3-N3-M1b
|
1 Participants
n=13 Participants
|
|
TNM staging
T4-N0-M1a
|
3 Participants
n=13 Participants
|
|
TNM staging
T4-N2-M0
|
1 Participants
n=13 Participants
|
|
TNM staging
T4-N3-M1a
|
1 Participants
n=13 Participants
|
|
TNM staging
T4-N3-M1b
|
1 Participants
n=13 Participants
|
|
Type of prior platinum treatment
Adjuvant
|
2 Participants
n=13 Participants
|
|
Type of prior platinum treatment
Advanced disease
|
11 Participants
n=13 Participants
|
PRIMARY outcome
Timeframe: at interim (after the first 9 pts have been followed for 12 weeks) & final analysis (approx. 40 months after inclusion of first pt)Population: The statistical design of the trial, included an interim efficacy analysis to be performed as soon as the 12-week status of the first 9 patients was available. So, the interim analysis was performed but up to then 13 patients have been enrolled.
Disease control (DC) is defined as complete or partial response, or disease stabilisation lasting at least 12 weeks. Disease control will be determined using RECIST 1.1 criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. Progression (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum recorded on the trial. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions denotes disease progression. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters recorded on the trial.
Outcome measures
| Measure |
Afatinib
n=13 Participants
Afatinib 40 mg p.o./day until tumour progression or lack of tolerability
|
|---|---|
|
Disease Control (Defined as Complete or Partial Response, or Disease Stabilisation Lasting at Least 12 Weeks)
Analysis of all enrolled patients (N=13) · DC at 12 weeks- "Yes"
|
7 Participants
|
|
Disease Control (Defined as Complete or Partial Response, or Disease Stabilisation Lasting at Least 12 Weeks)
Analysis of all enrolled patients (N=13) · DC at 12 weeks- "No"
|
6 Participants
|
|
Disease Control (Defined as Complete or Partial Response, or Disease Stabilisation Lasting at Least 12 Weeks)
Interim analysis patients (N=9) · DC at 12 weeks- "Yes"
|
4 Participants
|
|
Disease Control (Defined as Complete or Partial Response, or Disease Stabilisation Lasting at Least 12 Weeks)
Interim analysis patients (N=9) · DC at 12 weeks- "No"
|
5 Participants
|
SECONDARY outcome
Timeframe: Time assessed from the date of enrolment until documented progression or death (max 36 months)Population: All patients enrolled up to trial termination
Progression-free survival (PFS) is defined as the time from date of enrollment until documented progression or death, if progression is not documented. Censoring will occur at the last tumor assessment only if patients is lost to follow-up
Outcome measures
| Measure |
Afatinib
n=13 Participants
Afatinib 40 mg p.o./day until tumour progression or lack of tolerability
|
|---|---|
|
Progression-free Survival
|
15.9 weeks
Interval 6.0 to 35.4
|
SECONDARY outcome
Timeframe: Assessed across all time-points during the period from enrolment to termination of trial treatment (max. 36 months)Population: All patients enrolled in the trial up to trial termination. From the total of 13 patients, one patient had only one tumor assessment and was classified as "Non-Evaluable", since she cannot be accounted for the Objective Response rate.
Objective response is defined as best overall response (CR or PR) across all assessment time-points during the period from enrollment to termination of trial treatment. Objective response to afatinib treatment will be determined using RECIST 1.1 criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. Progression (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum recorded on the trial. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions denotes disease progression. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters recorded on the trial.
Outcome measures
| Measure |
Afatinib
n=13 Participants
Afatinib 40 mg p.o./day until tumour progression or lack of tolerability
|
|---|---|
|
Objective Response
Objective response (CR or PR)
|
1 Participants
|
|
Objective Response
Stable disease
|
6 Participants
|
|
Objective Response
Progression disease
|
5 Participants
|
|
Objective Response
Non-evaluable
|
1 Participants
|
SECONDARY outcome
Timeframe: Time assessed from the date of enrolment until death (max 36 months)Population: All patients enrolled in the trial up to trial termination
Overall survival (OS) is defined as the time from the date of enrollment until death from any cause. Censoring will occur at the last follow-up.
Outcome measures
| Measure |
Afatinib
n=13 Participants
Afatinib 40 mg p.o./day until tumour progression or lack of tolerability
|
|---|---|
|
Overall Survival
|
56.0 weeks
Interval 16.3 to 100.0
|
SECONDARY outcome
Timeframe: Assessed from the date of informed consent until 90 days after the final dose of afatinib (max 18 months).Population: All patients enrolled in the trial up to trial termination
Adverse events classified according to NCI CTCAE version 4.
Outcome measures
| Measure |
Afatinib
n=13 Participants
Afatinib 40 mg p.o./day until tumour progression or lack of tolerability
|
|---|---|
|
Toxicities of Treatment
Experienced AE/SAE
|
13 Participants
|
|
Toxicities of Treatment
No AE/SAE
|
0 Participants
|
Adverse Events
Afatinib
Serious adverse events
| Measure |
Afatinib
n=13 participants at risk
Afatinib 40 mg p.o./day until tumour progression or lack of tolerability
Afatinib: 40mg p.o./ day until documented progression or unacceptable toxicity
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Metabolism and nutrition disorders
Dehydration
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Renal and urinary disorders
Acute kidney injury
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Cardiac disorders
Pericardial effusion
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
Other adverse events
| Measure |
Afatinib
n=13 participants at risk
Afatinib 40 mg p.o./day until tumour progression or lack of tolerability
Afatinib: 40mg p.o./ day until documented progression or unacceptable toxicity
|
|---|---|
|
Gastrointestinal disorders
Diarrhea
|
84.6%
11/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Gastrointestinal disorders
Mucositis oral
|
30.8%
4/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Gastrointestinal disorders
Abdominal pain
|
23.1%
3/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Gastrointestinal disorders
Vomiting
|
23.1%
3/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
30.8%
4/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
30.8%
4/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
23.1%
3/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Infections and infestations
Paronyclia
|
38.5%
5/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
23.1%
3/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
General disorders
Fatigue
|
23.1%
3/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Gastrointestinal disorders
Constipation
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Gastrointestinal disorders
Dry mouth
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Gastrointestinal disorders
Nausea
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Skin and subcutaneous tissue disorders
Other
|
15.4%
2/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Infections and infestations
Bladder infection
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Infections and infestations
Eye infection
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Infections and infestations
Sinusitis
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Infections and infestations
Tooth infection
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Infections and infestations
Urinary track infection
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Infections and infestations
Nail infection
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Infections and infestations
Papulopustular rash
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Infections and infestations
Other (tonsillitis)
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
15.4%
2/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
General disorders
Flu like symptoms
|
15.4%
2/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
General disorders
Non-cardiac chest
|
15.4%
2/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
General disorders
Malaise
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Investigations
GGT increased
|
15.4%
2/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Investigations
Asparate aminotransferase increased
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Investigations
Creatine increased
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Investigations
Platelet count decreased
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Investigations
Weight loss
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Metabolism and nutrition disorders
Hyponatremia
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Musculoskeletal and connective tissue disorders
Arthalgia
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Nervous system disorders
Headache
|
15.4%
2/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Nervous system disorders
Dysgeusia
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Nervous system disorders
Other (paraplegia from Th4))
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Renal and urinary disorders
Cystitis noninfective
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Renal and urinary disorders
Urinary incontinence
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Renal and urinary disorders
Urinary track obstruction
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Blood and lymphatic system disorders
Anemia
|
15.4%
2/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Cardiac disorders
Ventricular arrhythmia
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Eye disorders
Dry eye
|
15.4%
2/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
|
Vascular disorders
Hypertension
|
7.7%
1/13 • From the date of informed consent until 90 days after the final dose of afatinib (max 18 months).
|
Additional Information
Heidi Roschitzki-Voser, Lead Trial Activities
European Thoracic Oncology Platform (ETOP)
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place