Brigatinib-5007
Research type
Research Study
Full title
A Cohort Study to Describe the Occurrence of Early-Onset Pulmonary Events in Patients with Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Treated with Brigatinib: A Post-Authorisation Safety Study
IRAS ID
283500
Contact name
Samreen Ahmed
Contact email
Sponsor organisation
Takeda Development Centre Americas Inc
Duration of Study in the UK
4 years, 6 months, 31 days
Research summary
Summary of Research: This is a non-interventional research study. The purpose of this study is to understand how the drug Alunbrig® (brigatinib) affects patient’s lungs, including any early-onset pulmonary events (EOPE), which are pulmonary side effects that often occur in the first 14 days after starting your treatment with Alunbrig®. This study will also examine how well patients understand the information presented to them in the Alunbrig® Patient Alert Card.
This study is sponsored by Takeda Development Centre Americas Inc, who will be referred to as the ‘Sponsor’. The Sponsor is paying the study clinic and the study doctor is to carry out this research study. Patients who have a specific type of non-small cell lung cancer (ALK+ advanced NSCLC) and their doctor has prescribed Alunbrig® to treat their disease may be invited to participate in this study.
Up to 180 patients will participate in this study, at approximately 35 sites in at least 10 countries in Europe. This study is expected to run until February 2024, though it may end earlier, depending on the number of patients recruited and the results analysed.
Participation in the study is expected to last 42 days after starting Alunbrig®. However, if participating patients have an EOPE within 14 days of receiving Alunbrig®, their study doctor may follow up with them for longer than 42 days. Data such as demographics, lifestyle data, medical history etc. will be collected during the study and after patients have consented in written. Patients will be asked to participate in a 15- 20 minute telephone interview to collect information on their receipt, understanding and use of the Alunbrig® Patient Alert Card.
The findings from this study may provide healthcare providers with important information for treating ALK+ advanced NSCLC with Alunbrig® in the future.
Lay summary of study results:
Brigatinib-5007 aimed to characterize the occurrence and risk factors of EOPEs(early-onset pulmonary event) and to assess the effectiveness of the brigatinib PAC(patient alert card) among ALK+(anaplastic lymphoma kinase-positive) advanced NSCLC(non-small cell lung cancer) patients newly treated with brigatinib in real-world practice. Out of 100 patients screened, 98 patients were enrolled to the study and included in the FAS(full analysis set)analysis. Half (n=49, 50.0%) of the enrolled patients were female and 60 (61.2%) patients were under the age of 65 years. In patients with disease stage information at study entry, 80 (88.9%) patients had Stage IV NSCLC(non-small cell lung cancer) at study entry, and approximately 10% had Stage IIIA (n=3) or IIIB (n=7).
During the entire study period, the predominant dose pattern was starting with 90mg daily dose then transitioned to 180mg daily (n=77, 78.6%), as per the recommended prescribing information. Out of the 94 (95.9%) patients with ‘Other’ reason for dose adjustment, 92 (97.9%) was due to ‘As per standard of care’.
The main findings showed that out of 98 ALK+(anaplastic lymphoma kinase-positive) advanced NSCLC(non-small cell lung cancer) patients newly treated with brigatinib enrolled in the study, 11 AESIs(adverse event of special interest) were reviewed by the adjudication committee. None of these AESIs(adverse event of special interest) were confirmed as EOPEs(early-onset pulmonary event). All AESIs(adverse event of special interest) were submitted to the adjudication committee, and the committee were able to request additional information to thoroughly evaluate each event and complete their assessment.
Of the 98 patients enrolled, 37 (37.8%) patients participated in the PAC(patient alert card) questionnaire interview.
Of the 37 responders of the PAC(patient alert card) questionnaire, 23 (62.2%) indicated that the patient received the PAC(patient alert card). Of those 23 PAC(patient alert card) recipients, 21 (91.3%) had read the PAC(patient alert card). Only 5 (13.5%) respondents demonstrated understanding of the PAC(patient alert card) by responding correctly to all 4 questions on “Understanding of the Alunbrig treatment” section. There were slight differences observed between age groups, which was particularly evident in the question pertaining to the potential for fever during brigatinib treatment, where only 2 (13.3%) out of 15 patients aged ≥65 years provided a correct response, while 10 (45.5%) out of 22 patients aged <65 years correctly answered the question.
Overall, 21 (56.8%) respondents had 2 of the 3 criteria (receipt, reading, and understanding of the PAC(patient alert card)). The threshold of success was defined as at least 75% reaching 2 of the 3 criteria was not achieved. The assessment of the PAC(patient alert card) effectiveness did not meet the threshold of 75% per the study protocol. More importantly, participation in the PAC(patient alert card) questionnaire interview was not mandatory, and more than half of the patients in the study declined to participate.Summary of Results: Brigatinib-5007 aimed to characterize the occurrence and risk factors of Early-onset Pulmonary Events (EOPEs) and to assess the effectiveness of the Brigatinib Patient Alert Card (PAC) among ALK+ (anaplastic lymphoma kinase-positive) advanced NSCLC (Non-Small Cell Lung Cancer) patients newly treated with Brigatinib in real-world practice. Out of 100 patients screened, 98 patients were enrolled to the study and included in the Full Analysis Set (FAS) analysis. Half (n=49, 50.0%) of the enrolled patients were female and 60 (61.2%) patients were under the age of 65 years. In patients with disease stage information at study entry, 80 (88.9%) patients had Stage IV NSCLC (non-small cell lung cancer) at study entry, and approximately 10% had Stage IIIA (n=3) or IIIB (n=7).
During the entire study period, the predominant dose pattern was starting with 90mg daily dose then transitioned to 180mg daily (n=77, 78.6%), as per the recommended prescribing information. Out of the 94 (95.9%) patients with ‘Other’ reason for dose adjustment, 92 (97.9%) was due to ‘As per standard of care’. The main findings showed that out of 98 ALK+ (Anaplastic Lymphoma Kinase-Positive) advanced NSCLC (Non-Small Cell Lung Cancer) patients newly treated with Brigatinib enrolled in the study, 11 adverse events of special interest (AESIs) were reviewed by the adjudication committee. None of these Adverse Events of Special Interest (AESIs) were confirmed as Early-Onset Pulmonary Events (EOPEs). All adverse event of special interest (AESIs) were submitted to the adjudication committee, and the committee were able to request additional information to thoroughly evaluate each event and complete their assessment.
Of the 98 patients enrolled, 37 (37.8%) patients participated in the Patient Alert Card (PAC) questionnaire interview.
Of the 37 responders of the Patient Alert Card (PAC) questionnaire, 23 (62.2%) indicated that the patient received the Patient Alert Card (PAC). Of those 23 Patient Alert Card (PAC) recipients, 21 (91.3%) had read the Patient Alert Card (PAC). Only 5 (13.5%) respondents demonstrated understanding of the Patient Alert Card (PAC) by responding correctly to all 4 questions on “Understanding of the Alunbrig treatment” section. There were slight differences observed between age groups, which was particularly evident in the question pertaining to the potential for fever during Brigatinib treatment, where only 2 (13.3%) out of 15 patients aged ≥65 years provided a correct response, while 10 (45.5%) out of 22 patients aged <65 years correctly answered the question.
Overall, 21 (56.8%) respondents had 2 of the 3 criteria (receipt, reading, and understanding of the Patient Alert Card (PAC). The threshold of success was defined as at least 75% reaching 2 of the 3 criteria was not achieved. The assessment of the Patient Alert Card (PAC) effectiveness did not meet the threshold of 75% per the study protocol. More importantly, participation in the Patient Alert Card (PAC) questionnaire interview was not mandatory, and more than half of the patients in the study declined to participate.
Brigatinib-5007 provides a more accurate representation of Early-onset Pulmonary Events (EOPE) incidence in the real-world compared to previous studies. All adverse event of special interest (AESI) were reviewed by an external adjudication committee that assessed and confirmed if the event is truly an Early-onset Pulmonary Events (EOPE). None of the 11 Adverse Events of Special Interest (AESI) were confirmed as early-onset pulmonary events (EOPEs) by the adjudication committee.
Almost all patients in the study received the appropriate dosage of Brigatinib as per standard of care. High relative dose intensity was observed in the study indicating that the lack of confirmed Early-onset Pulmonary Events (EOPE) was not attributable to underdosing. Although the assessment of Patient Alert Card (PAC) effectiveness did not meet the threshold per the study protocol, the participation in the Patient Alert Card (PAC) questionnaire interview was not mandatory, and more than half of the patients in the study declined to participate.
There were no confirmed Early-onset Pulmonary Events (EOPEs) or new safety findings in Brigatinib-5007. The safety profile in this study was consistent with the known safety profile of Brigatinib.REC name
South Central - Hampshire A Research Ethics Committee
REC reference
20/SC/0330
Date of REC Opinion
30 Sep 2020
REC opinion
Further Information Favourable Opinion