The Study Observes How Long Patients With Non-small Cell Lung Cancer (NSCLC) Benefit From Treatment With Epidermal Growth Factor Tyrosine Kinase Inhibitor (EGFR-TKI) When Given Either for Uncommon Mutations or for Common Mutations in the Sequence Afatinib Followed by Osimertinib

Study Overview
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Brief Summary
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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

Official Title
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UpSwinG: Real World Study on TKI Activity in Uncommon Mutations and Sequencing Giotrif®

Conditions
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Non-squamous, Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Afatinib (Gi(l)otrif®)
* Drug: Erlotinib (Tarceva®)
* Drug: Gefitinib (IRESSA®)
* Drug: Osimertinib (Tagrisso®)
* Drug: Afatinib (Gi(l)otrif®)
* Drug: Osimertinib (Tagrisso®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients Diagnosed with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFRTKI) naive advanced EGFR mutated non-small cell lung cancer (NSCLC), treated for Epidermal Growth Factor Receptor (EGFR) mutated NSCLC within regular clinical practice. 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: Patients harbouring uncommon or compound EGFR mutations 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 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: Patients treated for EGFR mutated NSCLC within a clinical trial or participated in GioTag study. Patients with active brain metastases at start of EGFR-TKI therapy (independent of treatment line) For uncommon mutation cohort: Patients treated with osimertinib with no further uncommon mutation than acquired T790M Further exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Uncommon EGFR mutation cohort<br>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. | Drug: Afatinib (Gi(l)otrif®)<br>* Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) as first or second-line therapy.<br>Drug: Erlotinib (Tarceva®)<br>* Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) as first or second-line therapy.<br>Drug: Gefitinib (IRESSA®)<br>* Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) as first or second-line therapy.<br>Drug: Osimertinib (Tagrisso®)<br>* Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) as first or second-line therapy.<br>|
| Sequencing cohort<br>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. | Drug: Afatinib (Gi(l)otrif®)<br>* As first line therapy.<br>Drug: Osimertinib (Tagrisso®)<br>* In the case the T790M resistance mutation was developed (second line therapy).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 13 years for Uncommon EGFR mutation cohort and up to 6 years for the Sequencing Cohort. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Up to 13 years. | 
| 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). | Up to 6 years. | 
| 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). | Up to 6 years. | 
| 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. | Up to 13 years for Uncommon EGFR mutation cohort and up to 6 years for the Sequencing Cohort. | 
| 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. | 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 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. | 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). | 
| 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). | From start of first-line treatment to stop of second-line or death by any cause, up to 13 years. | 
| 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. | 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 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. | 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). | 
| 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. | Up to 13 years. | 
| 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. | 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 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. | 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). | 
| 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. | Up to 13 years. | 
| 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). | At start of first-line chemotherapy before index line (i.e. between 2007 and 2019). | 
| 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). | At start of first-line chemotherapy before index line (i.e. between 2007 and 2019). |