Trial Outcomes & Findings for Afatinib Osimertinib Sequencing NIS (NCT NCT03370770)
NCT ID: NCT03370770
Last Updated: 2020-12-24
Results Overview
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.
Recruitment status
COMPLETED
Target enrollment
204 participants
Primary outcome timeframe
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.
Results posted on
2020-12-24
Participant Flow
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.
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.
Participant milestones
| Measure |
Patients With EGFR Mutation-positive NSCLC
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 Study
STARTED
|
204
|
|
Overall Study
COMPLETED
|
98
|
|
Overall Study
NOT COMPLETED
|
106
|
Reasons for withdrawal
| Measure |
Patients With EGFR Mutation-positive NSCLC
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 Study
Patient was followed in another hospital center
|
1
|
|
Overall Study
Progressive Disease
|
98
|
|
Overall Study
Adverse Event
|
2
|
|
Overall Study
Death
|
5
|
Baseline Characteristics
Afatinib Osimertinib Sequencing NIS
Baseline characteristics by cohort
| Measure |
Patients With EGFR Mutation-positive NSCLC
n=204 Participants
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).
|
|---|---|
|
Age, Continuous
|
60.1 Years
STANDARD_DEVIATION 10.48 • n=93 Participants
|
|
Sex: Female, Male
Female
|
110 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
94 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
19 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
181 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
50 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
18 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
120 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
13 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 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.Population: 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.
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.
Outcome measures
| Measure |
Patients With EGFR Mutation-positive NSCLC
n=204 Participants
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).
|
|---|---|
|
Time on Treatment With Afatinib (Gi(l)Otrif®) Followed by Osimertinib
First analysis
|
27.6 Months
Interval 25.9 to 31.3
|
|
Time on Treatment With Afatinib (Gi(l)Otrif®) Followed by Osimertinib
Extension analysis
|
27.7 Months
Interval 26.7 to 29.9
|
SECONDARY outcome
Timeframe: Data collected from start of treatment until data entry completion; up to 96.8 months.Population: Patients in the Full Analysis Set (FAS), who discontinued treatment and with positive test results (either EGFR sensitizing Mutation and/or T790M) available.
Different types of resistance mutations identified at the time of discontinuation of osimertinib treatment were systematically reviewed and categorised.
Outcome measures
| Measure |
Patients With EGFR Mutation-positive NSCLC
n=39 Participants
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).
|
|---|---|
|
The Percentage of Participants With Different Types of Mutations After Categorisation
T790M positive
|
69.2 Percentage of participants (%)
|
|
The Percentage of Participants With Different Types of Mutations After Categorisation
Loss of T790M
|
20.5 Percentage of participants (%)
|
|
The Percentage of Participants With Different Types of Mutations After Categorisation
T790M positive, loss of sensitizing mutation
|
10.3 Percentage of participants (%)
|
Adverse Events
Patients With EGFR Mutation-positive NSCLC
Serious events: 32 serious events
Other events: 62 other events
Deaths: 31 deaths
Serious adverse events
| Measure |
Patients With EGFR Mutation-positive NSCLC
n=203 participants at risk
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).
|
|---|---|
|
General disorders
Disease progression
|
13.3%
27/203 • 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.
Participants in the Full Analysis Set (FAS), who were included in the extension period.
|
|
General disorders
Death
|
0.49%
1/203 • 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.
Participants in the Full Analysis Set (FAS), who were included in the extension period.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.49%
1/203 • 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.
Participants in the Full Analysis Set (FAS), who were included in the extension period.
|
|
Infections and infestations
Sepsis
|
0.49%
1/203 • 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.
Participants in the Full Analysis Set (FAS), who were included in the extension period.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer
|
0.49%
1/203 • 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.
Participants in the Full Analysis Set (FAS), who were included in the extension period.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.49%
1/203 • 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.
Participants in the Full Analysis Set (FAS), who were included in the extension period.
|
Other adverse events
| Measure |
Patients With EGFR Mutation-positive NSCLC
n=203 participants at risk
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).
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
25.6%
52/203 • 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.
Participants in the Full Analysis Set (FAS), who were included in the extension period.
|
|
Gastrointestinal disorders
Stomatitis
|
10.3%
21/203 • 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.
Participants in the Full Analysis Set (FAS), who were included in the extension period.
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.7%
34/203 • 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.
Participants in the Full Analysis Set (FAS), who were included in the extension period.
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
5.9%
12/203 • 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.
Participants in the Full Analysis Set (FAS), who were included in the extension period.
|
|
Infections and infestations
Paronychia
|
12.3%
25/203 • 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.
Participants in the Full Analysis Set (FAS), who were included in the extension period.
|
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