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.

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT04647110

Enrollment

549

Registered

2020-11-30

Start date

2020-12-14

Completion date

2021-03-15

Last updated

2023-04-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

ALK-positive NSCLC

Brief summary

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

Interventions

DRUGcrizotinib

as provided in real world practice

DRUGalectinib

as provided in real world practice

DRUGbrigatinib

as provided in real world practice

DRUGceritinib

as provided in real world practice

DRUGlorlatinib

as provided in real world practice

Study design

Observational model

COHORT

Time perspective

RETROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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	6 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)	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.
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	5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)	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.
Percentage of Participants Alive After 6 Years From Index Date: Based on Treatment Cohort Groups	6 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)	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.
Percentage of Participants Alive After 6 Years From Index Date: 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)	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.
Percentage of Participants Alive After 6 Years From Index Date: Based on ALK Sequencing, 1 Line of ALK TKI Treatment	6 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)	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.
Percentage of Participants Alive After 6 Years From Index Date: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	6 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)	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.
Percentage of Participants Alive After 6 Years From Index Date: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	6 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)	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.
Percentage of Participants Alive After 6 Years From Index Date: 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)	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.
Overall Survival (OS): Based on Treatment Cohort Groups	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)	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.
Overall Survival: 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)	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.
Overall Survival: Based on Central Nervous System (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)	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.
Overall Survival: Based on ALK Sequencing, 1 Line of ALK TKI Treatment	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)	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.
Overall Survival: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	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)	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.
Overall Survival: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	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)	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.
Overall Survival: Based on ALK Sequencing, More Than or Equal to (>=) 4 Lines of ALK TKI Treatment	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)	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.
Percentage of Participants Alive After 5 Years From Index Date: Based on Treatment Cohort Groups	5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)	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.
Percentage of Participants Alive After 5 Years From Index Date: 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)	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.
Percentage of Participants Alive After 5 Years From Index Date: 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)	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.
Percentage of Participants Alive After 5 Years From Index Date: Based on ALK Sequencing, 1 Line of ALK TKI Treatment	5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)	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.
Percentage of Participants Alive After 5 Years From Index Date: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)	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.
Percentage of Participants Alive After 5 Years From Index Date: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)	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.

Secondary

Measure	Time frame	Description
Duration of Treatment: 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 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.
Duration of Treatment: Based on ALK Sequencing, 1 Line of ALK TKI Treatment	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 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.
Duration of Treatment: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	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 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.
Duration of Treatment: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	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 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.
Duration of Treatment: Based on ALK Sequencing, More Than or Equal to (>=) 4 Lines of ALK TKI Treatment	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 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.
Duration of Treatment: Based on Treatment Cohort Groups	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 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.

Countries

Sweden

Participant flow

Recruitment details

Study population included participants aged greater than or equal to 18 years at index date (date of first ALK TKI prescription), with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) who had at least one filled prescription of ALK tyrosine kinase inhibitors (TKI) registered in the Swedish Prescribed Drug Register, between 01-Jan-2012 to 31-Dec-2020. Data of eligible participants were assessed in approximately 3 months of this retrospective observational study.

Pre-assignment details

According to application sent to ethical counsel for this study, it was pre-planned not to report data for those cohorts/groups which had less than (\<) 5 participants at the index date. Hence, due to ethical compliance study team ensured results would only be displayed on an aggregate level for reporting arms having greater than or equal to (\>=) 5 participants at index date.

Participants by arm

Arm	Count
Participants With No First Line Chemotherapy Participants included in this arm received at least one filled prescription of ALK TKIs in real world practices, with no first line chemotherapy treatment. ALK TKIs were crizotinib, alectinib, brigatinib, ceritinib, or lorlatinib.	345
Participants With First Line Chemotherapy Participants included in this arm received at least one filled prescription of ALK TKIs in real world practices, along with first line chemotherapy treatment. ALK TKIs were crizotinib, alectinib, brigatinib, ceritinib, or lorlatinib.	204
Total	549

Baseline characteristics

Characteristic	Participants With No First Line Chemotherapy	Participants With First Line Chemotherapy	Total
Age, Continuous	63.08 Years STANDARD_DEVIATION 13.96	63.24 Years STANDARD_DEVIATION 13.28	63.13 Years STANDARD_DEVIATION 13.7
Race and Ethnicity Not Collected	—	—	0 Participants
Sex: Female, Male Female	189 Participants	112 Participants	301 Participants
Sex: Female, Male Male	156 Participants	92 Participants	248 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 0	0 / 0
other Total, other adverse events	0 / 0	0 / 0
serious Total, serious adverse events	0 / 0	0 / 0

Outcome results

Primary

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.

Time frame: 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)

Population: Analysis population included all eligible participants whose data were retrieved from Swedish administrative registers and assessed. Here, Overall Number of Participants Analyzed (N) signifies participants evaluable for this measure and received only 1 line of ALK TKIs with/ without chemotherapy. Due to ethical compliance, it was pre-planned not to report data for those reporting groups which had \<5 participants at the index date.

Arm	Measure	Value (MEDIAN)
Group A1	Overall Survival: Based on ALK Sequencing, 1 Line of ALK TKI Treatment	0.88 Years
Group A2	Overall Survival: Based on ALK Sequencing, 1 Line of ALK TKI Treatment	NA Years
Group B1	Overall Survival: Based on ALK Sequencing, 1 Line of ALK TKI Treatment	NA Years
Group B2	Overall Survival: Based on ALK Sequencing, 1 Line of ALK TKI Treatment	0.63 Years
Group C1	Overall Survival: Based on ALK Sequencing, 1 Line of ALK TKI Treatment	NA Years
Group C2	Overall Survival: Based on ALK Sequencing, 1 Line of ALK TKI Treatment	0.59 Years

Primary

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.

Population: Analysis population included all eligible participants whose data were retrieved from Swedish administrative registers and assessed. Overall Number of Participants Analyzed (N): participants evaluable for this measure and received only 2 lines of ALK TKIs with/ without chemotherapy. Groups with N =0: no participants with respective ALK TKI sequencing. Due to ethical compliance, it was pre-planned not to report data for those reporting groups which had \<5 participants at the index date.

Arm	Measure	Value (MEDIAN)
Group A1	Overall Survival: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	NA Years
Group B1	Overall Survival: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	1.27 Years
Group B2	Overall Survival: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	NA Years
Group C2	Overall Survival: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	NA Years
Group D1	Overall Survival: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	NA Years
Ceritinib + Lorlatinib	Overall Survival: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	NA Years
Crizotinib + Alectinib + Chemotherapy	Overall Survival: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	2.69 Years
Crizotinib + Brigatinib + Chemotherapy	Overall Survival: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	NA Years
Crizotinib + Ceritinib + Chemotherapy	Overall Survival: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	1.38 Years
Alectinib + Brigatinib + Chemotherapy	Overall Survival: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	NA Years
Alectinib + Ceritinib + Chemotherapy	Overall Survival: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	NA Years
Alectinib + Lorlatinib + Chemotherapy	Overall Survival: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	NA Years
Ceritinib + Alectinib + Chemotherapy	Overall Survival: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	NA Years

Primary

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.

Population: Analysis population included all eligible participants whose data were retrieved from Swedish administrative registers and assessed. Overall Number of Participants Analyzed (N): participants evaluable for this measure and received only 3 lines of ALK TKIs with/ without chemotherapy. Groups with N =0: no participants with respective ALK TKI sequencing. Due to ethical compliance, it was pre-planned not to report data for those reporting groups which had \<5 participants at the index date.

Arm	Measure	Value (MEDIAN)
Group A2	Overall Survival: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	5.41 Years
Group B1	Overall Survival: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	NA Years
Group B2	Overall Survival: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	2.78 Years
Group C1	Overall Survival: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	NA Years
Ceritinib + Brigatinib	Overall Survival: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	NA Years
Ceritinib + Lorlatinib	Overall Survival: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	NA Years
Crizotinib + Alectinib + Chemotherapy	Overall Survival: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	NA Years
Alectinib + Ceritinib + Chemotherapy	Overall Survival: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	NA Years
Alectinib + Lorlatinib + Chemotherapy	Overall Survival: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	NA Years
Ceritinib + Alectinib + Chemotherapy	Overall Survival: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	NA Years
Ceritinib + Brigatinib + Chemotherapy	Overall Survival: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	4.06 Years
Ceritinib + Lorlatinib + Chemotherapy	Overall Survival: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	NA Years
Crizotinib + Brigatinib + Lorlatinib + Chemotherapy	Overall Survival: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	NA Years

Primary

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.

Population: Analysis population included all eligible participants whose data were retrieved from Swedish administrative registers and assessed. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure and received \>= 4 lines of ALK TKI treatment with or without chemotherapy.

Arm	Measure	Value (MEDIAN)
Group A1	Overall Survival: Based on ALK Sequencing, More Than or Equal to (>=) 4 Lines of ALK TKI Treatment	5.49 Years
Group A2	Overall Survival: Based on ALK Sequencing, More Than or Equal to (>=) 4 Lines of ALK TKI Treatment	5.27 Years

Primary

Overall Survival: Based on Central Nervous System (CNS) Metastases Status

Population: Analysis population included all eligible participants whose data were retrieved from Swedish administrative registers and assessed.

Arm	Measure	Value (MEDIAN)
Group A1	Overall Survival: Based on Central Nervous System (CNS) Metastases Status	1.94 Years
Group A2	Overall Survival: Based on Central Nervous System (CNS) Metastases Status	0.61 Years

Primary

Overall Survival: Based on Chemotherapy Status

Population: Analysis population included all eligible participants whose data were retrieved from Swedish administrative registers and assessed.

Arm	Measure	Value (MEDIAN)
Group A1	Overall Survival: Based on Chemotherapy Status	2.02 Years
Group A2	Overall Survival: Based on Chemotherapy Status	1.44 Years

Primary

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.

Arm	Measure	Value (MEDIAN)
Group A1	Overall Survival (OS): Based on Treatment Cohort Groups	1.94 Years
Group A2	Overall Survival (OS): Based on Treatment Cohort Groups	2.30 Years
Group B1	Overall Survival (OS): Based on Treatment Cohort Groups	4.56 Years
Group B2	Overall Survival (OS): Based on Treatment Cohort Groups	2.94 Years
Group C1	Overall Survival (OS): Based on Treatment Cohort Groups	NA Years
Group C2	Overall Survival (OS): Based on Treatment Cohort Groups	5.41 Years
Group D1	Overall Survival (OS): Based on Treatment Cohort Groups	NA Years

Primary

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.

Time frame: 5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)

Population: Analysis population included all eligible participants whose data were retrieved from Swedish administrative registers and assessed. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure with a follow up of 5 years post index date. Reporting arm with Overall Number of Participants Analyzed = 0, signifies that no participant had a follow up of 5 years post index date.

Arm	Measure	Value (NUMBER)
Group A1	Percentage of Participants Alive After 5 Years From Index Date: Based on ALK Sequencing, 1 Line of ALK TKI Treatment	11.43 Percentage of participants
Group B2	Percentage of Participants Alive After 5 Years From Index Date: Based on ALK Sequencing, 1 Line of ALK TKI Treatment	0.00 Percentage of participants

Primary

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.

Time frame: 5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)

Population: Analysis population included all eligible participants whose data were retrieved from Swedish administrative registers and assessed. Here, Overall Number of Participants Analyzed (N) signifies participants who evaluable for this measure with a follow up of 5 years post index date. Reporting groups with N =0 signifies that no participant had a follow up of 5 years post index date.

Arm	Measure	Value (NUMBER)
Group A1	Percentage of Participants Alive After 5 Years From Index Date: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	66.67 Percentage of participants
Group B1	Percentage of Participants Alive After 5 Years From Index Date: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	0.00 Percentage of participants
Crizotinib + Alectinib + Chemotherapy	Percentage of Participants Alive After 5 Years From Index Date: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	0.00 Percentage of participants
Crizotinib + Ceritinib + Chemotherapy	Percentage of Participants Alive After 5 Years From Index Date: Based on ALK Sequencing, 2 Lines of ALK TKI Treatment	7.14 Percentage of participants

Primary

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.

Time frame: 5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)

Population: Analysis population included all eligible participants whose data were retrieved from Swedish administrative registers and assessed. Here, Overall Number of Participants Analyzed (N) signifies participants who evaluable for this measure with a follow up of 5 years post index date. Reporting groups with N =0 signifies that no participant had a follow up of 5 years post index date.

Arm	Measure	Value (NUMBER)
Group A2	Percentage of Participants Alive After 5 Years From Index Date: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	100.00 Percentage of participants
Group B2	Percentage of Participants Alive After 5 Years From Index Date: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	50.00 Percentage of participants
Ceritinib + Brigatinib + Chemotherapy	Percentage of Participants Alive After 5 Years From Index Date: Based on ALK Sequencing, 3 Lines of ALK TKI Treatment	25.00 Percentage of participants

Primary

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.

Time frame: 5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)

Arm	Measure	Value (NUMBER)
Group A1	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	100.00 Percentage of participants
Group A2	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	100.00 Percentage of participants

Primary

Percentage of Participants Alive After 5 Years From Index Date: Based on Chemotherapy Status

Time frame: 5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)

Arm	Measure	Value (NUMBER)
Group A1	Percentage of Participants Alive After 5 Years From Index Date: Based on Chemotherapy Status	16.39 Percentage of participants
Group A2	Percentage of Participants Alive After 5 Years From Index Date: Based on Chemotherapy Status	16.39 Percentage of participants

Primary

Percentage of Participants Alive After 5 Years From Index Date: Based on CNS Metastases Status

Time frame: 5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)

Arm	Measure	Value (NUMBER)
Group A1	Percentage of Participants Alive After 5 Years From Index Date: Based on CNS Metastases Status	17.24 Percentage of participants
Group A2	Percentage of Participants Alive After 5 Years From Index Date: Based on CNS Metastases Status	0.00 Percentage of participants

Primary

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.

Time frame: 5 years post index date during data identification period of 9 years (retrieved data assessed in this observational study for approximately 3 months)

Population: Analysis population included all eligible participants whose data were retrieved from Swedish administrative registers and assessed. Here, Overall Number of Participants Analyzed (N) signifies participants who evaluable for this measure with a follow up of 5 years post index date. Reporting groups with N =0 signifies that no participant had a follow up of 5 years post index date.

Arm	Measure	Value (NUMBER)
Group A1	Percentage of Participants Alive After 5 Years From Index Date: Based on Treatment Cohort Groups	6.25 Percentage of participants
Group A2	Percentage of Participants Alive After 5 Years From Index Date: Based on Treatment Cohort Groups	9.52 Percentage of participants
Group B1	Percentage of Participants Alive After 5 Years From Index Date: Based on Treatment Cohort Groups	40.00 Percentage of participants
Group B2	Percentage of Participants Alive After 5 Years From Index Date: Based on Treatment Cohort Groups	50.00 Percentage of participants
Group C1	Percentage of Participants Alive After 5 Years From Index Date: Based on Treatment Cohort Groups	66.67 Percentage of participants
Group C2	Percentage of Participants Alive After 5 Years From Index Date: Based on Treatment Cohort Groups	100 Percentage of participants

Primary

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.