Brigatinib-5010 Study
Research type
Research Study
Full title
Real-World Treatment Patterns and Effectiveness of Subsequent Treatments Following Frontline Brigatinib for Patients with ALK+ NSCLC: A Multisite Retrospective Chart Review Study
IRAS ID
318016
Contact name
Sharmistha Ghosh
Contact email
Sponsor organisation
Takeda Pharmaceuticals U.S.A., Inc.
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
0 years, 8 months, 1 days
Research summary
Research Summary:
Lung cancer is the second most-commonly diagnosed cancer. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Approximately 4-5% of all NSCLC cases is the Anaplastic Lymphoma Kinase enzyme positive disease (ALK +). Most ALK+ patients tend to present with locally advanced or metastatic disease at time of diagnosis, which may reflect the aggressiveness of these tumors.
The treatment landscape for ALK+ NSCLC has been evolving in recent years.
Several trials have shown progression-free survival benefits of 2nd-generation ALK inhibitors including brigatinib, over 1st-generation crizotinib in the frontline setting.
In the ALTA-1L trial, brigatinib has shown superior clinical efficacy compared to crizotinib. However, limited information on the subsequent anti-cancer therapy was collected under the trial protocol. Little is known regarding the subsequent treatments post frontline brigatinib after the end of the trial, appropriate subsequent treatments for patients who progressed on frontline brigatinib have not been well defined. No studies have evaluated the managing patterns and outcomes of the subsequent treatments post frontline brigatinib in a real-world setting.
To address these data gaps, Brigatinib-5010 non-interventional retrospective study aims to generate real-world data to assess the subsequent treatments post frontline brigatinib for the ALK+ NSCLC patients, previously enrolled in the ALTA-1L trial.
Study will be conducted at the NHS Sites, participated in ALTA-1 study and have enrolled patients in the brigatinib treatment arm.
Brigatinib-5010 is the chart abstraction study, representing simple approach to observing patients’ experience on subsequent treatments following their participation in ALTA-1L. Data of interest will be abstracted from established medical records of patients. The objective of this study is to examine treatment patterns, sequencing, clinical outcomes, and healthcare resource utilization associated with the subsequent treatments post frontline brigatinib. Data collection will start in Q3 2022 2022; final analysis is planned in Q2 of 2023.Summary of research:
This multicentre retrospective study used data from patients’ medical records to examine treatment patterns, management, and clinical outcomes of patients post frontline Brigatinib in real-world setting. Overall, patients in this study had a similar distribution on demographic and clinical characteristics compared to the Brigatinib arm of the ALTA-1L trial. The BIRC (blinded, independent review committees) - assessed PFS (Progression Free Survival) in both studies indicated a potentially more ill patient population in the Brigatinib-5010 study compared to patients in the Brigatinib arm of the ALTA-1L trial who did not discontinue frontline Brigatinib.
Patients who received subsequent ALK TKI (anaplastic lymphoma kinase tyrosine kinase inhibitor) treatment after frontline Brigatinib were observed to have a prolonged clinical benefit compared to patients who did not receive subsequent ALK TKI (anaplastic lymphoma kinase tyrosine kinase inhibitor) treatment. Additionally, patients who responded to frontline Brigatinib seems to be more responsive to subsequent treatment, with a numerically higher median OS (overall Survival) among patients who achieved CR (Complete response) or PR (Partial Response) to frontline Brigatinib compared to those who did not achieve CR(Complete response) or PR (Partial Response).
The rwPFS (real-world progression-free survival) results from the study seems to indicate potentially better real-world efficacy for lorlatinib compared to non-lorlatinib ALK TKIs post frontline Brigatinib, particularly among patients with brain metastases at index. In this subgroup of patients, a numerically higher median rwPFS and rwPFS2 (real-world progression-free survival) was observed among patients who received 2LoT (2nd Line of Treatment) lorlatinib compared to those who received 2LoT (2nd Line of Treatment) non-lorlatinib ALK TKIs (anaplastic lymphoma kinase tyrosine kinase inhibitor). It is important to note that the study is descriptive and is not powered to detect differences between treatment and subgroups.
Regarding safety, the AE profile in this study was comparable to the overall existing safety profile of Brigatinib (including findings reported in ALTA-1L trial). There was no new additional safety signal observed.
The findings in this study suggest that Brigatinib is an effective frontline treatment choice followed by other ALK TKIs (anaplastic lymphoma kinase tyrosine kinase inhibitor), including lorlatinib.REC name
London - Fulham Research Ethics Committee
REC reference
22/PR/1291
Date of REC Opinion
28 Oct 2022
REC opinion
Favourable Opinion