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

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

Study Overview

• Status: Completed
• Conditions: ALK-positive NSCLC
• Intervention / Treatment: Drug: crizotinib; Drug: alectinib; Drug: brigatinib; Drug: ceritinib; Drug: lorlatinib

• Study Type: Observational
• Enrollment (Actual): 549

Contacts and Locations

Study Locations

• Sweden
  • Sollentuna, Sweden, 19190
    • Pfizer Innovations AB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adult patients treated with ALK TKIs in Sweden between 2012 and 2019, identified via the national prescription register.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Swedish Anaplastic lymphoma kinase (ALK) positive Non-small cell lung cancer (NSCLC) patients	Drug: crizotinib; as provided in real world practice; Drug: alectinib; as provided in real world practice; Drug: brigatinib; as provided in real world practice; Drug: ceritinib; as provided in real world practice; Drug: lorlatinib; as provided in real world practice

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2020
• Primary Completion (Actual): March 15, 2021
• Study Completion (Actual): March 15, 2021

Study Registration Dates

• First Submitted: November 25, 2020
• First Submitted That Met QC Criteria: November 25, 2020
• First Posted (Actual): November 30, 2020

Study Record Updates

• Last Update Posted (Actual): April 6, 2023
• Last Update Submitted That Met QC Criteria: April 4, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Crizotinib; Ceritinib
• Other Study ID Numbers: B7461035; SEQUIA (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No