Non-squamous, Non-Small Cell Lung Cancer
Conditions
Brief summary
Non-interventional, multi-country, multi-centre cohort study based on existing data from medical records (paper or electronic) or electronic health records of patients with advanced NSCLC harbouring EGFR mutations and treated with an EGFR-TKI
Interventions
DRUGAfatinib (Gi(l)otrif®)
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) as first or second-line therapy.
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) as first or second-line therapy.
DRUGGefitinib (IRESSA®)
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) as first or second-line therapy.
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) as first or second-line therapy.
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult patients 2. Diagnosed with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFRTKI) naive advanced EGFR mutated non-small cell lung cancer (NSCLC), 3. treated for Epidermal Growth Factor Receptor (EGFR) mutated NSCLC within regular clinical practice. 4. Informed and privacy consent signature must be obtained depending on local regulations. More specific inclusion criteria for each cohort are the following: Uncommon mutation cohort: 5. Patients harbouring uncommon or compound EGFR mutations 6. Patients who started with either afatinib (Gi(l)otrif®), gefitinib (Iressa®), erlotinib (Tarceva®), or osimertinib (Tagrisso®) in the first- or second-line setting within regular clinical practice 7. Patients must have started EGFR-TKI treatment at least 12 months prior to data entry. Sequencing cohort: 5\. Patients with common EGFR mutations (Del19, L858R) 6. Patients were treated with afatinib (Gi(l)otrif®) in the first-line setting and for acquired T790M mutation with osimertinib in the second line; 7. Patients must have started osimertinib treatment at least 10 months prior to data entry. Patients treated with osimertinib within an early access program/ compassionate use program (EAP/CUP) are allowed
Exclusion criteria
1. Patients treated for EGFR mutated NSCLC within a clinical trial or participated in GioTag study. 2. Patients with active brain metastases at start of EGFR-TKI therapy (independent of treatment line) 3. For uncommon mutation cohort: Patients treated with osimertinib with no further uncommon mutation than acquired T790M Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time on Treatment With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) | Up to 13 years for Uncommon EGFR mutation cohort and up to 6 years for the Sequencing Cohort. | Uncommon Mutation Cohort: Time on treatment with EGFR-TKI assessed as the time from start of EGFR-TKI treatment until the end of treatment or death by any cause is reported. Common mutation cohort: Time on treatment with EGFR-TKI assessed as the time from start of afatinib (Gi(l)otrif®) as first-line treatment until the end of the second line treatment (the last dose of osimertinib) or death date by any cause. Time on treatment was analysed using Kaplan-Meier method, and the median was tabulated along with two-sided 95% confidence interval using the Greenwood's variance estimate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sequencing Cohort: Overall Response Rate to First Line Afatinib | Up to 6 years. | Overall response rate (ORR) using RECIST criteria as assessed by investigator. Overall response rate to first line afatinib treatment for the Common Epidermal Growth Factor Receptor (EGFR) mutation cohort is reported. (ORR is defined as number of patients with complete or partial response evaluated by Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1)). (Per RECIST 1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR). |
| Sequencing Cohort: Overall Response Rate to Second-line Treatment Osimertinib | Up to 6 years. | Overall response rate (ORR) using RECIST criteria as assessed by investigator. Overall response rate to second-line treatment (Osimertinib) is reported. (ORR is defined as number of patients with complete or partial response evaluated by Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1)). (Per RECIST 1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR). |
| Overall Survival | Up to 13 years for Uncommon EGFR mutation cohort and up to 6 years for the Sequencing Cohort. | Uncommon Mutation Cohort: Overall survival since index line treatment start of Tyrosine Kinase Inhibitor (TKI) medication administered per generation until death date by any cause or the end of index line is reported. Sequencing cohort: Overall survival for since first-line afatinib treatment start until death date by any cause or the end of index line. Kaplan-Meier estimates of quartiles of time to death were computed (with their 95% Confidence Intervals, using Greenwood's variance estimate. |
| Number of Participants for Each Type of Biological Samples Used for Mutation Detection at First Line Treatment Start | At first-line treatment start (i.e. between 2007 and 2019 for the Uncommon Epidermal Growth Factor Receptor (EGFR) mutation cohort and between 2014 and 2018 for Sequencing Cohort). | Number of participants for each type of biological samples used for mutation detection at first line treatment start is reported. The reported types of biological samples are: * Tissue, histological sample (solid biopsy); * Cytological sample; * Blood (liquid biopsy); * Other and * Unknown. |
| Number of Participants for Each Category of Methodology Used for Mutational Testing at First Line Treatment Start | At first-line treatment start (i.e. between 2007 and 2019 for the Uncommon Epidermal Growth Factor Receptor (EGFR) mutation cohort and between 2014 and 2018 for the Sequencing Cohort). | Number of participants for each type of methodologies used for mutational testing is reported. The reported types of methodology are: * Amplification Refractory Mutation System (ARMS); * Polymerase Chain reactions (PCR)-based techniques; * Sequencing; * Next-Generation Sequencing (NGS); * Other; * Unknown. |
| Uncommon Mutation Cohort: Time on Treatment Until Failure of Second-line (TTF2) | From start of first-line treatment to stop of second-line or death by any cause, up to 13 years. | Time on treatment until failure of second-line (TTF2), defined as time elapsed from start of first-line treatment (regardless the type of treatment) to stop of second-line (regardless of the type of treatment) or death by any cause is reported. Kaplan-Meier estimates of quartiles of time to second-line treatment failure were computed (with their 95% Confidence Intervals, using Greenwood's variance estimate). |
| Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Start | At second-line treatment start (i.e. between 2007 and 16-Jul-2020 for Uncommon EGFR mutation cohort and between 2014 and 23-Oct-2020 for the Sequencing Cohort | Number of participants for each type of biological samples used for mutation detection at second line treatment start is reported. The reported types of biological samples are: * Tissue, Histological sample (solid biopsy); * Cytological sample; * Blood (liquid biopsy); * Not applicable-Clinical evaluation; * Other; * Unknown. Not applicable - Clinical evaluation: The uncommon Epidermal Growth Factor Receptor (EGFR) mutational status had become available after Progression on conventional second-line therapy. Erlotinib was given as state of the art second-line therapy in 2014, and an EGFR mutation was clinically suspected due to the Long-Lasting response. However, due to the unavailability of tumor tissue, this could be proven only after liquid biopsy had subsequently become available at the center in 2016. For the Sequencing cohort second-line treatment start is initiated by the beginning of the therapy with Osimertinib. |
| Uncommon Epidermal Growth Factor Receptor (EGFR) Mutation Cohort: Overall Response Rate to Index Line Treatment | Up to 13 years. | Overall response rate (ORR) using RECIST criteria as assessed by investigator. ORR to index line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) treatment is reported (ORR is defined as number of patients with complete or partial response evaluated by Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1)). (Per RECIST 1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR). |
| Uncommon Cohort: Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Index Therapy Start | Up to 13 years. | Number of participants for each type of biological samples used for mutation detection at index therapy start (index therapy refers to therapy switch from first-line chemotherapy to second-line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) therapy (index line)) is reported. The reported categories of biological samples are: * Tissue, Histological sample (solid biopsy); * Cytological sample; * Blood (liquid biopsy); * Other and * Unknown. |
| Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Start | At second-line treatment start (i.e. between 2007 and 16-Jul-2020 for Uncommon Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR) mutation cohort and between 2014 and 23-Oct-2020 for the Sequencing Cohort). | Number of participants for each type of methodology used for mutational testing at second-line treatment start is reported. The reported types of methodologies are: * Amplification Refractory Mutation System (ARMS); * Polymerase Chain Reaction (PCR)-based techniques; * Sequencing; * Next-Generation Sequencing (NGS); * Other; * Unknown/Not applicable- Clinical evaluation. |
| Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Stop/End of Observation | At second-line treatment stop/end of observation (i.e. between 2007 and 16-Jul-2020 for Uncommon Epidermal Growth Factor Receptor (EGFR) mutation cohort and between 2014 and 23-Oct-2020 for the Sequencing Cohort). | Number of participants for each type of methodology used for mutational testing is reported. The reported types of methodologies are: * Polymerase Chain Reaction (PCR)-based techniques; * Next-Generation Sequencing (NGS); * Unknown. |
| Uncommon Mutation Cohort: Number of Participants for Each Type of Methodology Used for Mutation Detection at Index Therapy Start | Up to 13 years. | Number of participants for each type of methodology used for mutation detection at index therapy start is reported. Index therapy refers to therapy switch from first-line chemotherapy to second-line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) therapy (index line). The reported categories of methodology are: * Amplification Refractory Mutation System (ARMS), * Polymerase chain reaction based techniques (PCR-based techniques), * Sequencing, * Next-Generation Sequencing (NGS), * Unknown. |
| Uncommon Mutation Cohort: Number of Participants for Each Type of Methodology Used for Mutation Detection at Start of First-line Chemotherapy Before Index Line | At start of first-line chemotherapy before index line (i.e. between 2007 and 2019). | Number of participants for each type of methodology used for mutation detection at start of first-line chemotherapy before index line is reported. The reported types of methodologies are: * PCR-based techniques; * Sequencing; * Next-Generation Sequencing (NGS); * Unknown. Index therapy refers to therapy switch from first-line chemotherapy to second-line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) therapy (index line). |
| Uncommon Mutation Cohort: Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Start of First-line Chemotherapy Before Index Line | At start of first-line chemotherapy before index line (i.e. between 2007 and 2019). | Number of participants for each type of biological samples used for mutation detection at start of first-line chemotherapy before index line is reported. Index therapy refers to therapy switch from first-line chemotherapy to second-line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) therapy (index line). The reported types of biological samples are: * Tissue, Histological sample (solid biopsy); * Cytological sample, Blood (liquid biopsy). |
| Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Stop/End of Observation | At second-line treatment start (i.e. between 2007 and 16-Jul-2020 for Uncommon Epidermal Growth Factor Receptor (EGFR) mutation cohort and between 2014 and 23-Oct-2020 for the Sequencing Cohort). | Number of participants for each type of biological samples used for mutation detection at second line treatment stop/end of observation is reported. The reported categories of biological samples are: * Tissue, Histological sample (solid biopsy); * Cytological sample; * Blood (liquid biopsy); * Other. |
Countries
United Kingdom
Participant flow
Recruitment details
A Real world, non-interventional study based on existing data from medical records or electronic health records. The study aimed to collect more information on the benefit of individual Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs) treatment for the uncommon mutations and the overall benefit for the sequential EGFR TKI treatment with afatinib and osimertinib for the common EGFR mutations on patients with Non-Small Cell Lung Cancer (NSCLC).
Pre-assignment details
Every patient who fulfilled inclusion and exclusion criteria and agreed to participate in the study was selected until the required sample size was achieved. Deceased and untraceable patients were enrolled whenever possible and discussed with the local authorities.
Participants by arm
| Arm | Count |
|---|---|
| Uncommon EGFR Mutation Cohort This arm included patients with Non-Small Cell Lung Cancer (NSCLC) carrying uncommon mutations in the epidermal growth factor receptor (EGFR) who were treated with the following Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs) as first or second-line therapy:
* 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®).
* Erlotinib (Tarceva®): 25mg or 100mg or 150mg tablet once daily as indicated in the approved labels of erlotinib (Tarceva®).
* Gefitinib (IRESSA®): 250mg tablet once daily as indicated in the approved labels of gefitinib (IRESSA®).
* Osimertinib (Tagrisso®): 80 mg or 40 mg tablets once daily as indicated in the approved labels of osimertinib).
In the first- or second-line with a threshold of start of treatment of at least 12 months respectively prior to data entry. | 246 |
| Sequencing Cohort This arm included Non-Small Cell Lung Cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation positive who received the following treatment sequence:
\- 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®) as first line therapy, in the case the T790M resistance mutation was developed (second line therapy) the patients received osimertinib (Tagrisso®): 80 mg or 40 mg tablets once daily as indicated in the approved labels of osimertinib; the threshold of start of osimertinib at least 10 months prior to data entry. | 191 |
| Total | 437 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Patients not harbouring uncommon or compound EGFR mutations | 3 | 0 |
| Overall Study | Patients not starting osimertinib treatment at least 10 months prior to data entry | 0 | 4 |
| Overall Study | Patients not treated with afatinib in first-line or with osimertinib in second line | 0 | 8 |
| Overall Study | Patients treated for EGFR mutated NSCLC within a clinical trial | 3 | 0 |
| Overall Study | Patients treated for EGFR mutated NSCLC within a clinical trial or participated in GioTag study | 0 | 1 |
| Overall Study | Patients who did not start EGFR-TKI treatment at least 12 months prior to data entry | 1 | 0 |
| Overall Study | Patients with active brain metastases at start of EGFR-TKI therapy | 2 | 0 |
| Overall Study | Patients with active brain metastases at start of EGFR-TKI therapy (independent of treatment line) | 0 | 2 |
| Overall Study | Patients without common EGFR mutations (Del19, L858R) | 0 | 1 |
Baseline characteristics
| Characteristic | Sequencing Cohort | Total | Uncommon EGFR Mutation Cohort |
|---|---|---|---|
| Age, Continuous | 61.4 Years STANDARD_DEVIATION 11.7 | 64.89 Years STANDARD_DEVIATION 11.3 | 67.6 Years STANDARD_DEVIATION 11 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 118 Participants | 324 Participants | 206 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 15 Participants | 32 Participants | 17 Participants |
| Race (NIH/OMB) White | 55 Participants | 78 Participants | 23 Participants |
| Sex: Female, Male Female | 106 Participants | 244 Participants | 138 Participants |
| Sex: Female, Male Male | 85 Participants | 193 Participants | 108 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 35 |
| other Total, other adverse events | 41 / 44 | 30 / 35 |
| serious Total, serious adverse events | 12 / 44 | 6 / 35 |
Outcome results
Primary
Time on Treatment With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI)
Uncommon Mutation Cohort: Time on treatment with EGFR-TKI assessed as the time from start of EGFR-TKI treatment until the end of treatment or death by any cause is reported. Common mutation cohort: Time on treatment with EGFR-TKI assessed as the time from start of afatinib (Gi(l)otrif®) as first-line treatment until the end of the second line treatment (the last dose of osimertinib) or death date by any cause. Time on treatment was analysed using Kaplan-Meier method, and the median was tabulated along with two-sided 95% confidence interval using the Greenwood's variance estimate.
Time frame: Up to 13 years for Uncommon EGFR mutation cohort and up to 6 years for the Sequencing Cohort.
Population: Eligible Patients set (Uncommon mutation cohort): All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable.~Eligible Patients set (Sequencing cohort): All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Uncommon EGFR Mutation Cohort | Time on Treatment With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) | 9.89 Months |
| Sequencing Cohort | Time on Treatment With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) | 27.7 Months |
Secondary
Number of Participants for Each Category of Methodology Used for Mutational Testing at First Line Treatment Start
Number of participants for each type of methodologies used for mutational testing is reported. The reported types of methodology are: * Amplification Refractory Mutation System (ARMS); * Polymerase Chain reactions (PCR)-based techniques; * Sequencing; * Next-Generation Sequencing (NGS); * Other; * Unknown.
Time frame: At first-line treatment start (i.e. between 2007 and 2019 for the Uncommon Epidermal Growth Factor Receptor (EGFR) mutation cohort and between 2014 and 2018 for the Sequencing Cohort).
Population: Eligible Patients set (Uncommon mutation cohort): All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable.~Eligible Patients set (Sequencing cohort): All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Category of Methodology Used for Mutational Testing at First Line Treatment Start | Amplification Refractory Mutation System (ARMS) | 4 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Category of Methodology Used for Mutational Testing at First Line Treatment Start | PCR-based techniques | 155 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Category of Methodology Used for Mutational Testing at First Line Treatment Start | Sequencing | 39 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Category of Methodology Used for Mutational Testing at First Line Treatment Start | Next-Generation Sequencing (NGS) | 20 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Category of Methodology Used for Mutational Testing at First Line Treatment Start | Unknown | 42 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Category of Methodology Used for Mutational Testing at First Line Treatment Start | Other | 0 Participants |
| Sequencing Cohort | Number of Participants for Each Category of Methodology Used for Mutational Testing at First Line Treatment Start | Unknown | 41 Participants |
| Sequencing Cohort | Number of Participants for Each Category of Methodology Used for Mutational Testing at First Line Treatment Start | Amplification Refractory Mutation System (ARMS) | 4 Participants |
| Sequencing Cohort | Number of Participants for Each Category of Methodology Used for Mutational Testing at First Line Treatment Start | Next-Generation Sequencing (NGS) | 8 Participants |
| Sequencing Cohort | Number of Participants for Each Category of Methodology Used for Mutational Testing at First Line Treatment Start | PCR-based techniques | 122 Participants |
| Sequencing Cohort | Number of Participants for Each Category of Methodology Used for Mutational Testing at First Line Treatment Start | Other | 1 Participants |
| Sequencing Cohort | Number of Participants for Each Category of Methodology Used for Mutational Testing at First Line Treatment Start | Sequencing | 15 Participants |
Secondary
Number of Participants for Each Type of Biological Samples Used for Mutation Detection at First Line Treatment Start
Number of participants for each type of biological samples used for mutation detection at first line treatment start is reported. The reported types of biological samples are: * Tissue, histological sample (solid biopsy); * Cytological sample; * Blood (liquid biopsy); * Other and * Unknown.
Time frame: At first-line treatment start (i.e. between 2007 and 2019 for the Uncommon Epidermal Growth Factor Receptor (EGFR) mutation cohort and between 2014 and 2018 for Sequencing Cohort).
Population: Eligible Patients set (Uncommon mutation cohort): All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable.~Eligible Patients set (Sequencing cohort): All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at First Line Treatment Start | Cytological sample | 32 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at First Line Treatment Start | Other | 2 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at First Line Treatment Start | Blood (liquid biopsy) | 3 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at First Line Treatment Start | Unknown | 3 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at First Line Treatment Start | Tissue, Histological sample (solid biopsy) | 212 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at First Line Treatment Start | Unknown | 6 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at First Line Treatment Start | Tissue, Histological sample (solid biopsy) | 160 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at First Line Treatment Start | Cytological sample | 19 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at First Line Treatment Start | Blood (liquid biopsy) | 6 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at First Line Treatment Start | Other | 2 Participants |
Secondary
Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Start
Number of participants for each type of biological samples used for mutation detection at second line treatment start is reported. The reported types of biological samples are: * Tissue, Histological sample (solid biopsy); * Cytological sample; * Blood (liquid biopsy); * Not applicable-Clinical evaluation; * Other; * Unknown. Not applicable - Clinical evaluation: The uncommon Epidermal Growth Factor Receptor (EGFR) mutational status had become available after Progression on conventional second-line therapy. Erlotinib was given as state of the art second-line therapy in 2014, and an EGFR mutation was clinically suspected due to the Long-Lasting response. However, due to the unavailability of tumor tissue, this could be proven only after liquid biopsy had subsequently become available at the center in 2016. For the Sequencing cohort second-line treatment start is initiated by the beginning of the therapy with Osimertinib.
Time frame: At second-line treatment start (i.e. between 2007 and 16-Jul-2020 for Uncommon EGFR mutation cohort and between 2014 and 23-Oct-2020 for the Sequencing Cohort
Population: Eligible Patients set: All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable and who were initiated on a second line treatment. For the Uncommon EGFR mutation cohort only patients with \>1 Non-Small Cell Lung Cancer (NSCLC) with re-evaluated mutational status.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Start | Tissue, Histological sample (solid biopsy) | 22 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Start | Cytological sample | 3 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Start | Blood (liquid biopsy) | 8 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Start | Other | 0 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Start | Unknown | 0 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Start | Not applicable - Clinical evaluation | 1 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Start | Not applicable - Clinical evaluation | 0 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Start | Unknown | 19 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Start | Cytological sample | 18 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Start | Tissue, Histological sample (solid biopsy) | 93 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Start | Blood (liquid biopsy) | 57 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Start | Other | 7 Participants |
Secondary
Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Stop/End of Observation
Number of participants for each type of biological samples used for mutation detection at second line treatment stop/end of observation is reported. The reported categories of biological samples are: * Tissue, Histological sample (solid biopsy); * Cytological sample; * Blood (liquid biopsy); * Other.
Time frame: At second-line treatment start (i.e. between 2007 and 16-Jul-2020 for Uncommon Epidermal Growth Factor Receptor (EGFR) mutation cohort and between 2014 and 23-Oct-2020 for the Sequencing Cohort).
Population: Eligible Patients set: All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable. For the Uncommon EGFR mutation cohort eligible patients with \>1 Non-Small Cell Lung Cancer (NSCLC) line with re-evaluated mutational status are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Stop/End of Observation | Tissue, Histological sample (solid biopsy) | 5 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Stop/End of Observation | Blood (liquid biopsy) | 4 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Stop/End of Observation | Other | 1 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Stop/End of Observation | Cytological sample | 0 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Stop/End of Observation | Cytological sample | 1 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Stop/End of Observation | Tissue, Histological sample (solid biopsy) | 9 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Stop/End of Observation | Other | 0 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Second Line Treatment Stop/End of Observation | Blood (liquid biopsy) | 9 Participants |
Secondary
Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Start
Number of participants for each type of methodology used for mutational testing at second-line treatment start is reported. The reported types of methodologies are: * Amplification Refractory Mutation System (ARMS); * Polymerase Chain Reaction (PCR)-based techniques; * Sequencing; * Next-Generation Sequencing (NGS); * Other; * Unknown/Not applicable- Clinical evaluation.
Time frame: At second-line treatment start (i.e. between 2007 and 16-Jul-2020 for Uncommon Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR) mutation cohort and between 2014 and 23-Oct-2020 for the Sequencing Cohort).
Population: Eligible Patients set: All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable and who were initiated on a second line treatment. For the Uncommon EGFR mutation cohort only patients with \>1 Non-Small Cell Lung Cancer (NSCLC) with re-evaluated mutational status.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Start | PCR-based techniques | 23 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Start | Sequencing | 2 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Start | Next-Generation Sequencing (NGS) | 3 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Start | Unknown/Not applicable- Clinical evaluation | 6 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Start | Amplification Refractory Mutation System (ARMS) | 0 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Start | Other | 0 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Start | Amplification Refractory Mutation System (ARMS) | 3 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Start | PCR-based techniques | 121 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Start | Unknown/Not applicable- Clinical evaluation | 51 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Start | Sequencing | 2 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Start | Other | 1 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Start | Next-Generation Sequencing (NGS) | 13 Participants |
Secondary
Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Stop/End of Observation
Number of participants for each type of methodology used for mutational testing is reported. The reported types of methodologies are: * Polymerase Chain Reaction (PCR)-based techniques; * Next-Generation Sequencing (NGS); * Unknown.
Time frame: At second-line treatment stop/end of observation (i.e. between 2007 and 16-Jul-2020 for Uncommon Epidermal Growth Factor Receptor (EGFR) mutation cohort and between 2014 and 23-Oct-2020 for the Sequencing Cohort).
Population: Eligible Patients set: All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Stop/End of Observation | PCR-based techniques | 7 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Stop/End of Observation | Next-Generation Sequencing (NGS) | 2 Participants |
| Uncommon EGFR Mutation Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Stop/End of Observation | Unknown | 1 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Stop/End of Observation | PCR-based techniques | 11 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Stop/End of Observation | Next-Generation Sequencing (NGS) | 2 Participants |
| Sequencing Cohort | Number of Participants for Each Type of Methodology Used for Mutational Testing at Second-line Treatment Stop/End of Observation | Unknown | 3 Participants |
Secondary
Overall Survival
Uncommon Mutation Cohort: Overall survival since index line treatment start of Tyrosine Kinase Inhibitor (TKI) medication administered per generation until death date by any cause or the end of index line is reported. Sequencing cohort: Overall survival for since first-line afatinib treatment start until death date by any cause or the end of index line. Kaplan-Meier estimates of quartiles of time to death were computed (with their 95% Confidence Intervals, using Greenwood's variance estimate.
Time frame: Up to 13 years for Uncommon EGFR mutation cohort and up to 6 years for the Sequencing Cohort.
Population: Eligible Patients set (Uncommon mutation cohort): All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable. Eligible Patients set (Sequencing cohort): All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Uncommon EGFR Mutation Cohort | Overall Survival | 24.44 Months |
| Sequencing Cohort | Overall Survival | 36.50 Months |
Secondary
Sequencing Cohort: Overall Response Rate to First Line Afatinib
Overall response rate (ORR) using RECIST criteria as assessed by investigator. Overall response rate to first line afatinib treatment for the Common Epidermal Growth Factor Receptor (EGFR) mutation cohort is reported. (ORR is defined as number of patients with complete or partial response evaluated by Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1)). (Per RECIST 1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR).
Time frame: Up to 6 years.
Population: Eligible Patients set (Sequencing cohort): All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Uncommon EGFR Mutation Cohort | Sequencing Cohort: Overall Response Rate to First Line Afatinib | 131 Participants |
Secondary
Sequencing Cohort: Overall Response Rate to Second-line Treatment Osimertinib
Overall response rate (ORR) using RECIST criteria as assessed by investigator. Overall response rate to second-line treatment (Osimertinib) is reported. (ORR is defined as number of patients with complete or partial response evaluated by Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1)). (Per RECIST 1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR).
Time frame: Up to 6 years.
Population: Eligible Patients set (Sequencing cohort): All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Uncommon EGFR Mutation Cohort | Sequencing Cohort: Overall Response Rate to Second-line Treatment Osimertinib | 75 Participants |
Secondary
Uncommon Cohort: Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Index Therapy Start
Number of participants for each type of biological samples used for mutation detection at index therapy start (index therapy refers to therapy switch from first-line chemotherapy to second-line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) therapy (index line)) is reported. The reported categories of biological samples are: * Tissue, Histological sample (solid biopsy); * Cytological sample; * Blood (liquid biopsy); * Other and * Unknown.
Time frame: Up to 13 years.
Population: Eligible Patients set: All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable. 16 patients in the Uncommon EGFR mutation cohort who switched from first-line chemotherapy to second-line EGFR-TKI therapy for which EGFR mutational status was not re-evaluated at start of second-line treatment were not included in this group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Uncommon EGFR Mutation Cohort | Uncommon Cohort: Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Index Therapy Start | Tissue, Histological sample (solid biopsy) | 199 Participants |
| Uncommon EGFR Mutation Cohort | Uncommon Cohort: Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Index Therapy Start | Cytological sample | 29 Participants |
| Uncommon EGFR Mutation Cohort | Uncommon Cohort: Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Index Therapy Start | Blood (liquid biopsy) | 2 Participants |
| Uncommon EGFR Mutation Cohort | Uncommon Cohort: Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Index Therapy Start | Other | 2 Participants |
| Uncommon EGFR Mutation Cohort | Uncommon Cohort: Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Index Therapy Start | Unknown | 3 Participants |
Secondary
Uncommon Epidermal Growth Factor Receptor (EGFR) Mutation Cohort: Overall Response Rate to Index Line Treatment
Overall response rate (ORR) using RECIST criteria as assessed by investigator. ORR to index line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) treatment is reported (ORR is defined as number of patients with complete or partial response evaluated by Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1)). (Per RECIST 1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR).
Time frame: Up to 13 years.
Population: Eligible Patients set (Uncommon mutation cohort): All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Uncommon EGFR Mutation Cohort | Uncommon Epidermal Growth Factor Receptor (EGFR) Mutation Cohort: Overall Response Rate to Index Line Treatment | 96 Participants |
Secondary
Uncommon Mutation Cohort: Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Start of First-line Chemotherapy Before Index Line
Number of participants for each type of biological samples used for mutation detection at start of first-line chemotherapy before index line is reported. Index therapy refers to therapy switch from first-line chemotherapy to second-line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) therapy (index line). The reported types of biological samples are: * Tissue, Histological sample (solid biopsy); * Cytological sample, Blood (liquid biopsy).
Time frame: At start of first-line chemotherapy before index line (i.e. between 2007 and 2019).
Population: Eligible Patients set: All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable. Only patients switching from first-line chemotherapy to second-line EGFR-TKI therapy (index line) for which EGFR mutational status was not re-evaluated at start of second-line treatment are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Uncommon EGFR Mutation Cohort | Uncommon Mutation Cohort: Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Start of First-line Chemotherapy Before Index Line | Tissue, Histological sample (solid biopsy) | 13 Participants |
| Uncommon EGFR Mutation Cohort | Uncommon Mutation Cohort: Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Start of First-line Chemotherapy Before Index Line | Cytological sample | 3 Participants |
| Uncommon EGFR Mutation Cohort | Uncommon Mutation Cohort: Number of Participants for Each Type of Biological Samples Used for Mutation Detection at Start of First-line Chemotherapy Before Index Line | Blood (liquid biopsy) | 1 Participants |
Secondary
Uncommon Mutation Cohort: Number of Participants for Each Type of Methodology Used for Mutation Detection at Index Therapy Start
Number of participants for each type of methodology used for mutation detection at index therapy start is reported. Index therapy refers to therapy switch from first-line chemotherapy to second-line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) therapy (index line). The reported categories of methodology are: * Amplification Refractory Mutation System (ARMS), * Polymerase chain reaction based techniques (PCR-based techniques), * Sequencing, * Next-Generation Sequencing (NGS), * Unknown.
Time frame: Up to 13 years.
Population: Eligible Patients set: All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable. 16 patients in the Uncommon EGFR mutation cohort who switched from first-line chemotherapy to second-line EGFR-TKI therapy for which EGFR mutational status was not re-evaluated at start of second-line treatment were not included in this group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Uncommon EGFR Mutation Cohort | Uncommon Mutation Cohort: Number of Participants for Each Type of Methodology Used for Mutation Detection at Index Therapy Start | Amplification Refractory Mutation System (ARMS) | 4 Participants |
| Uncommon EGFR Mutation Cohort | Uncommon Mutation Cohort: Number of Participants for Each Type of Methodology Used for Mutation Detection at Index Therapy Start | PCR-based techniques | 146 Participants |
| Uncommon EGFR Mutation Cohort | Uncommon Mutation Cohort: Number of Participants for Each Type of Methodology Used for Mutation Detection at Index Therapy Start | Sequencing | 34 Participants |
| Uncommon EGFR Mutation Cohort | Uncommon Mutation Cohort: Number of Participants for Each Type of Methodology Used for Mutation Detection at Index Therapy Start | Next-Generation Sequencing (NGS) | 18 Participants |
| Uncommon EGFR Mutation Cohort | Uncommon Mutation Cohort: Number of Participants for Each Type of Methodology Used for Mutation Detection at Index Therapy Start | Unknown | 41 Participants |
Secondary
Uncommon Mutation Cohort: Number of Participants for Each Type of Methodology Used for Mutation Detection at Start of First-line Chemotherapy Before Index Line
Number of participants for each type of methodology used for mutation detection at start of first-line chemotherapy before index line is reported. The reported types of methodologies are: * PCR-based techniques; * Sequencing; * Next-Generation Sequencing (NGS); * Unknown. Index therapy refers to therapy switch from first-line chemotherapy to second-line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) therapy (index line).
Time frame: At start of first-line chemotherapy before index line (i.e. between 2007 and 2019).
Population: Eligible Patients set: All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable. Only patients switching from first-line chemotherapy to second-line EGFR-TKI therapy (index line) for which EGFR mutational status was not re-evaluated at start of second-line treatment are reported.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Uncommon EGFR Mutation Cohort | Uncommon Mutation Cohort: Number of Participants for Each Type of Methodology Used for Mutation Detection at Start of First-line Chemotherapy Before Index Line | PCR-based techniques | 9 Participants |
| Uncommon EGFR Mutation Cohort | Uncommon Mutation Cohort: Number of Participants for Each Type of Methodology Used for Mutation Detection at Start of First-line Chemotherapy Before Index Line | Sequencing | 5 Participants |
| Uncommon EGFR Mutation Cohort | Uncommon Mutation Cohort: Number of Participants for Each Type of Methodology Used for Mutation Detection at Start of First-line Chemotherapy Before Index Line | Next-Generation Sequencing (NGS) | 2 Participants |
| Uncommon EGFR Mutation Cohort | Uncommon Mutation Cohort: Number of Participants for Each Type of Methodology Used for Mutation Detection at Start of First-line Chemotherapy Before Index Line | Unknown | 1 Participants |
Secondary
Uncommon Mutation Cohort: Time on Treatment Until Failure of Second-line (TTF2)
Time on treatment until failure of second-line (TTF2), defined as time elapsed from start of first-line treatment (regardless the type of treatment) to stop of second-line (regardless of the type of treatment) or death by any cause is reported. Kaplan-Meier estimates of quartiles of time to second-line treatment failure were computed (with their 95% Confidence Intervals, using Greenwood's variance estimate).
Time frame: From start of first-line treatment to stop of second-line or death by any cause, up to 13 years.
Population: Eligible Patients set (Uncommon mutation cohort): All enrolled patients meeting all the inclusion and exclusion criteria to be evaluable and who were initiated on a second line treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Uncommon EGFR Mutation Cohort | Uncommon Mutation Cohort: Time on Treatment Until Failure of Second-line (TTF2) | 14.46 Months |