GIOTRIF in First Line Therapy of Advanced NSCLC With EGFR-mutations

Study Overview
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Brief Summary
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This observational study will investigate the efficacy, safety, tolerability and symptom control of GIOTRIF (Afatinib) in daily routine first-line therapy in patients with locally advanced or metastatic NSCLC harboring EGFR-mutations. Eligible NSCLC patients, for whom the treating physician has decided to initiate treatment with GIOTRIF in first line according to the local label, will be followed up for approximately 24 months.

Detailed Description
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Study Design:

Official Title
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An Observational Study of GIOTRIF (Afatinib) for First Line Therapy in Patients With Advanced Non Small Cell Lung Cancer (NSCLC) Harboring Epidermal Growth Factor Receptor (EGFR)-Mutations.

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Afatinib


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: EGFR- tyrosine kinase inhibitor (TKI) naive patients with histologically confirmed locally advanced or metastatic NSCLC with activating EGFR-mutations Age >= 18 years No diagnostic or therapeutic measures beyond routine clinical practice are required Patients for whom the treating physician has decided to initiate treatment with GIOTRIF Written informed consent prior inclusion Exclusion criteria: Contraindication for Afatinib according to the Summary of Product characteristics Participation in another clinical study until 30 days after end of treatment Prior systemic chemotherapy (Neo-/adjuvant therapy is permitted) Previous treatment with an EGFR-tyrosine kinase inhibitor Patients not willing or not able to fill in quality of life questionnaires Patients with missing or impaired legal capacity Pregnancy

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 |
| --- | --- |
| Afatinib<br> | Drug: Afatinib<br>* 50, 40, 30 or 20 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) Rate After 12 Months | The rate (probability) of being progression free after 12 months. PFS is defined as the time from first administration of the trial drug until objective tumor progression or death. The rate is the Kaplan-Meier estimated percent probability. | After 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective response rate is calculated as a percentage of participants with complete response (CR) or partial response (PR) (i.e CR+PR) as best unconfirmed response. Here CR and PR were determined by investigators by using RECIST/WHO/clinical evidence as investigators deemed appropriate. | From the initial dose of study drug until end of the treatment period, up to 48 months. | 
| Disease Control Rate (DCR) | Percentage of participants with controlled disease (CR + PR + stable disease (SD)) as best unconfirmed response. CR, PR and SD were determined by investigators by using RECIST/WHO/clinical evidence as investigators deemed appropriate | From the initial dose of study drug until end of the treatment period, up to 48 months. | 
| Progression Free Survival (PFS) | PFS was measured from start of therapy until progression or death, whichever came first. Progression was defined as the minimum of the first examination with progression and the date of progression documented by the treating physician. One day was added to the corresponding date. Patients without documented progression and not known to have died were censored at their date of last examination and one day was added. Median was derived by Kaplan Meier methods. | From first administration of the trial drug until objective tumour progression or death, up to 48 months. | 
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Percentage of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs). | From first administration of the trial drug until 30 days end after permanent discontinuation of therapy or end of study, up to 48 months. | 
| Toxicity and Side-effect Profile: Incidence of Diarrhea, Skin Reactions, Stomatitis and Paronychia | Toxicity and side-effect profile: incidence of diarrhea, skin reactions, stomatitis and paronychia. Skin reactions: acne, dermatitis acneiform, dry skin, pruritus, rash, rash maculo-papular, rash pustular. | From first administration of the trial drug until 30 days end after permanent discontinuation of therapy or end of study, up to 48 months. | 
| Treatment Duration | Duration of treatment with afatinib is calculated as Date of last administration + 1 day - Date of first administration. | From the initial dose of study drug until end of the treatment period, up to 48 months. | 
| Symptom Control - Time to Worsening (Cough, Dyspnea and Pain) | Symptom control was evaluated for cough, dyspnea and pain. Time to deterioration was calculated from date of baseline European Organisation for Research and Treatment of Cancer (EORTC) questionnaire until date of the EORTC questionnaire, where the first deterioration was measured. Patients without deterioration were censored at their date of last answered EORTC questionnaire, where the corresponding scale is evaluable. Participants had to select one answer on a scale ranging from 1=Not at All to 4=Very Much for questions 1 to 28 and 31 to 43 and on scale ranging from 1=Very Bad to 7=Excellent for questions 29 and 30. Afterwards, these scale scores were linearly transformed such that all scales ranged from 0 to 100, where higher scores represented higher level of symptoms. | Up to 48 months | 
| Percentage of Participants With Treatment Modification | Percentage of participants with treatment modification was calculated as percentage of participants with any dose reduction, dose escalation or any modification. | From the initial dose of study drug until end of the treatment period, up to 48 months. |