Real-world Therapy of ALK-positive NSCLC in Sweden: the Sequencing of ALK Tyrosine Kinase Inhibitor Drugs and Their Therapeutic Outcomes Based on Data From National Registers.

Study Overview
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Brief Summary
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This study aims to explore for the first time how the different ALK TKIs have been sequenced in real-world clinical practice and with which outcomes for Swedish lung cancer patients

Official Title
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Real-world Study of Non-small Cell Lung Cancer Treatment With ALK-tyrosine Kinase Inhibitors (ALK TKI) in Sweden: Drug Sequencing, Treatment Duration and Overall Survival - A Retrospective Study Using Swedish Register Data

Conditions
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ALK-positive NSCLC

Intervention / Treatment
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* Drug: crizotinib
* Drug: alectinib
* Drug: brigatinib
* Drug: ceritinib
* Drug: lorlatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: -Inclusion criteria for ALK-positive NSCLC patients will be based on prescription data i.e. defines eligible patients as adult patients with at least one filled prescription of ALK-inhibitors identified by the national prescription register. Only prescriptions filled at pharmacies can be captured in prescription registers, as they do not include data on hospital drugs. ALK-inhibitor treatments for patients with NSCLC are given primarily outside of the hospital setting minimizing the selection bias under the inclusion criteria. Exclusion Criteria: -not applicable

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 |
| --- | --- |
| Swedish Anaplastic lymphoma kinase (ALK) positive Non-small cell lung cancer (NSCLC) patients<br> | Drug: crizotinib<br>* as provided in real world practice<br>Drug: alectinib<br>* as provided in real world practice<br>Drug: brigatinib<br>* as provided in real world practice<br>Drug: ceritinib<br>* as provided in real world practice<br>Drug: lorlatinib<br>* as provided in real world practice<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS): Based on Treatment Cohort Groups | OS was defined as the time from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data). Kaplan-Meier method was used for analysis. Results were reported for treatment cohort groups based on generation of ALK treatment and were as following: Group A1 = chemotherapy + crizotinib (first generation ALK TKI) + any second (2nd) generation ALK TKI; Group A2 = crizotinib + any 2nd generation ALK TKI; Group B1: chemotherapy + crizotinib + any 2nd generation ALK TKI + any other 2nd generation ALK TKI; Group B2 = crizotinib + any 2nd generation ALK TKI + any other 2nd generation ALK TKI; Group C1 = chemotherapy + crizotinib + any 2nd generation ALK TKI + lorlatinib (third generation ALK TKI); Group C2: crizotinib + any 2nd generation ALK TKI + lorlatinib and Group D1 = any 2nd generation ALK TKI + any other 2nd generation ALK TKI. | From index date to the date of death due to any cause or censoring date, during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Overall Survival: Based on Chemotherapy Status | OS was defined as the time from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data). Kaplan-Meier method was used for analysis. Results were reported based on chemotherapy status. | From index date to the date of death due to any cause or censoring date, during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Overall Survival: Based on Central Nervous System (CNS) Metastases Status | OS was defined as the time from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data). Kaplan-Meier method was used for analysis. In this outcome measure, participants were grouped on basis of their CNS-metastases status. | From index date to the date of death due to any cause or censoring date, during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Overall Survival: Based on ALK Sequencing, 1 Line of ALK TKI Treatment | OS was defined as the time from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data). Kaplan-Meier method was used for analysis. In this outcome measure, OS was reported for participants who received 1 line of ALK TKI treatment. Reporting arms were based on type of ALK TKI, with or without chemotherapy. ALK TKIs considered were crizotinib, alectinib, ceritinib. | From index date to the date of death due to any cause or censoring date, during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Overall Survival: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment | OS was defined as the time from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data). Kaplan-Meier method was used for analysis. In this outcome measure OS was reported for participants who received 2 lines of ALK TKI treatment. Reporting arms were based on type of first line ALK TKI treatment and second line of ALK TKI treatment, with or without chemotherapy. | From index date to the date of death due to any cause or censoring date, during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Overall Survival: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment | OS was defined as the time from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data). Kaplan-Meier method was used for analysis. In this outcome measure OS was reported for participants who received 3 lines of ALK inhibitor treatment. Reporting arms were based on type of first line ALK TKI treatment, second line of ALK TKI treatment and third line of ALK TKI treatment with or without, chemotherapy. | From index date to the date of death due to any cause or censoring date, during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Overall Survival: Based on ALK Sequencing, More Than or Equal to (>=) 4 Lines of ALK TKI Treatment | OS was defined as the time from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data). Kaplan-Meier method was used for analysis. In this outcome measure, OS was reported for participants who received >=4 lines of ALK inhibitor treatment with or without chemotherapy. | From index date to the date of death due to any cause or censoring date, during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Percentage of Participants Alive After 5 Years From Index Date: Based on Treatment Cohort Groups | Results were reported for treatment cohort groups based on generation of ALK treatment and were as following: Group A1 = chemotherapy + crizotinib (first generation ALK TKI) + any second (2nd) generation ALK TKI; Group A2 = crizotinib + any 2nd generation ALK TKI; Group B1: chemotherapy + crizotinib + any 2nd generation ALK TKI + any other 2nd generation ALK TKI; Group B2 = crizotinib + any 2nd generation ALK TKI + any other 2nd generation ALK TKI; Group C1 = chemotherapy + crizotinib + any 2nd generation ALK TKI + lorlatinib (third generation ALK TKI); Group C2: crizotinib + any 2nd generation ALK TKI + lorlatinib and Group D1 = any 2nd generation ALK TKI + any other 2nd generation ALK TKI. | 5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Percentage of Participants Alive After 5 Years From Index Date: Based on Chemotherapy Status | Participants alive after five years from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data), were reported in this outcome measure. Results were reported based on chemotherapy status. | 5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Percentage of Participants Alive After 5 Years From Index Date: Based on CNS Metastases Status | Participants alive after five years from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data), were reported in this outcome measure. Results were reported based on CNS metastases status. | 5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Percentage of Participants Alive After 5 Years From Index Date: Based on ALK Sequencing, 1 Line of ALK TKI Treatment | Participants alive after five years from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data), were reported. In this outcome measure, participants who received 1 line of ALK TKI treatment, were reported. Reporting arms were based on type of first line ALK TKI treatment, with or without chemotherapy. ALK TKIs considered were crizotinib, alectinib, ceritinib. | 5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Percentage of Participants Alive After 5 Years From Index Date: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment | Participants alive after five years from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data), were reported. In this outcome measure, participants who received 2 lines of ALK TKI treatment, were reported. Reporting arms were based on type of first line ALK TKI treatment and second line of ALK TKI treatment, with or without chemotherapy. | 5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Percentage of Participants Alive After 5 Years From Index Date: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment | Participants alive after five years from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data), were reported. In this outcome measure, participants who received 3 lines of ALK TKI treatment. Reporting arms were based on type of first line ALK TKI treatment, second line of ALK TKI treatment, and third line of ALK TKI treatment, with or without chemotherapy. | 5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Percentage of Participants Alive After 5 Years From Index Date: Based on ALK Sequencing, More Than or Equal to (>=) 4 Lines of ALK TKI Treatment | Participants alive after five years from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data), were reported. In this outcome measure, data is reported for participants who received >=4 lines of ALK inhibitor treatment with or without chemotherapy. | 5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Percentage of Participants Alive After 6 Years From Index Date: Based on Treatment Cohort Groups | Results were reported for treatment cohort groups based on generation of ALK treatment and were as following: Group A1 = chemotherapy + crizotinib (first generation ALK TKI) + any second (2nd) generation ALK TKI; Group A2 = crizotinib + any 2nd generation ALK TKI; Group B1: chemotherapy + crizotinib + any 2nd generation ALK TKI + any other 2nd generation ALK TKI; Group B2 = crizotinib + any 2nd generation ALK TKI + any other 2nd generation ALK TKI; Group C1 = chemotherapy + crizotinib + any 2nd generation ALK TKI + lorlatinib (third generation ALK TKI); Group C2: crizotinib + any 2nd generation ALK TKI + lorlatinib and Group D1 = any 2nd generation ALK TKI + any other 2nd generation ALK TKI. | 6 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Percentage of Participants Alive After 6 Years From Index Date: Based on Chemotherapy Status | Participants alive after six years from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data), were reported in this outcome measure. Results were reported based on chemotherapy status. | 6 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Percentage of Participants Alive After 6 Years From Index Date: Based on CNS Metastases Status | Participants alive after six years from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data), were reported in this outcome measure. Results were reported based on CNS metastases status. | 6 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Percentage of Participants Alive After 6 Years From Index Date: Based on ALK Sequencing, 1 Line of ALK TKI Treatment | Participants alive after six years from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data), were reported. In this outcome measure, participants who received 1 line of ALK TKI treatment, were reported. Reporting arms were based on type of first line ALK TKI treatment, with or without chemotherapy. ALK TKIs considered were crizotinib, alectinib, ceritinib. | 6 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Percentage of Participants Alive After 6 Years From Index Date: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment | Participants alive after six years from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data), were reported. In this outcome measure, participants who received 2 lines of ALK TKI treatment, were reported. Reporting arms were based on type of first line ALK TKI treatment and second line of ALK TKI treatment, with or without chemotherapy. | 6 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Percentage of Participants Alive After 6 Years From Index Date: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment | Participants alive after six years from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data), were reported. In this outcome measure OS was reported for participants who received 3 lines of ALK inhibitor treatment. Reporting arms were based on type of first line ALK TKI treatment, second line of ALK TKI treatment, and third line of ALK TKI treatment, with or without chemotherapy. | 6 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Percentage of Participants Alive After 6 Years From Index Date: Based on ALK Sequencing, More Than or Equal to (>=) 4 Lines of ALK TKI Treatment | Participants alive after six years from index date (date of first ALK TKI prescription) to the date of death due to any cause or censoring date (latest available date in data), were reported. In this outcome measure, data is reported for participants who received >=4 lines of ALK inhibitor treatment with or without chemotherapy. | 6 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Treatment: Based on Treatment Cohort Groups | Duration of treatment was defined as number of days on treatment calculated based on pharmaceutical specialties in Sweden (FASS) recommended dose for filled prescriptions of ALK-inhibitors taking permissible gap and stockpiling into account. Results were reported for treatment cohort groups based on generation of ALK treatment and were as following: Group A1 = chemotherapy + crizotinib (first generation ALK TKI) + any second (2nd) generation ALK TKI; Group A2 = crizotinib + any 2nd generation ALK TKI; Group B1: chemotherapy + crizotinib + any 2nd generation ALK TKI + any other 2nd generation ALK TKI; Group B2 = crizotinib + any 2nd generation ALK TKI + any other 2nd generation ALK TKI; Group C1 = chemotherapy + crizotinib + any 2nd generation ALK TKI + lorlatinib (third generation ALK TKI); Group C2: crizotinib + any 2nd generation ALK TKI + lorlatinib and Group D1 = any 2nd generation ALK TKI + any other 2nd generation ALK TKI. | From index date to treatment completion/discontinuation during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Duration of Treatment: Based on Chemotherapy Status | Duration of treatment was defined as number of days on treatment calculated based on pharmaceutical specialties in Sweden (FASS) recommended dose for filled prescriptions of ALK-inhibitors taking permissible gap and stockpiling into account. Results were reported based on chemotherapy status. | From index date to treatment completion/discontinuation during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Duration of Treatment: Based on ALK Sequencing, 1 Line of ALK TKI Treatment | Duration of treatment was defined as number of days on treatment calculated based on FASS recommended dose for filled prescriptions of ALK-inhibitors taking permissible gap and stockpiling into account. Reporting arms were based on type of ALK TKI, with or without chemotherapy. ALK TKIs considered were crizotinib, alectinib, ceritinib. | From index date to treatment completion/discontinuation during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Duration of Treatment: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment | Duration of treatment was defined as number of days on treatment calculated based on FASS recommended dose for filled prescriptions of ALK-inhibitors taking permissible gap and stockpiling into account. Reporting arms were based on type of first line ALK TKI treatment, and second line of ALK TKI treatment, with or without chemotherapy. | From index date to treatment completion/discontinuation during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Duration of Treatment: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment | Duration of treatment was defined as number of days on treatment calculated based on FASS recommended dose for filled prescriptions of ALK-inhibitors taking permissible gap and stockpiling into account. Reporting arms were based on type of first line ALK TKI treatment, second line of ALK TKI treatment, and third line of ALK TKI treatment with or without chemotherapy. | From index date to treatment completion/discontinuation during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) | 
| Duration of Treatment: Based on ALK Sequencing, More Than or Equal to (>=) 4 Lines of ALK TKI Treatment | Duration of treatment was defined as number of days on treatment calculated based on FASS recommended dose for filled prescriptions of ALK-inhibitors taking permissible gap and stockpiling into account. In this outcome measure, duration of treatment was reported for participants who received >=4 lines of ALK inhibitor treatment, with or without chemotherapy. | From index date to treatment completion/discontinuation during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months) |