A Retrospective Non Interventional Study on First Line Treatment for Patients With BRAFV600E Mutant Metastatic Colorectal Cancer (mCRC)

Study Overview
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Brief Summary
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The presence of a BRAFV600E mutation is considered a marker of poor prognosis in patients with mCRC, and findings from clinical trials have largely remained inconclusive regarding the efficacy of first line treatments for BRAF-mutant mCRC patients. In the absence of targeted/specific treatment for BRAF-mutant mCRC, treatment practices can vary based on local practices and guidelines. There is, therefore, an unmet need to document the current practices for first-line treatment of BRAF-mutant mCRC, and their effectiveness and safety in a real-world setting. This real-world, multicenter non-interventional study (NIS) will describe the treatment patterns, effectiveness and safety of current treatment regimens in BRAFV600E mutant mCRC patients in Europe, with the aim to put the clinical study findings of the ongoing Phase 2, single-arm, open label trial (ANCHOR) into context of the current treatment landscape excluding investigational therapies. Additionally, the NIS output may be used to support future health technology assessment submissions and publications.

Detailed Description
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This retrospective, multi-center longitudinal study on BRAFV600E mutant mCRC patients will be conducted in Europe to characterize the first-line treatment patterns. All BRAFV600E mutant patients having initiated a first-line treatment for mCRC between January 1st, 2016 and December 31st, 2018 (both days inclusive) with drugs registered for mCRC in respective country will be eligible to participate. The study will not provide or recommend any treatment or procedure; all decisions regarding treatment are made at the sole discretion of the treating physician in accordance with their usual practices and all eligible patients will be considered for enrollment. The target countries for patient enrollment will include Germany, France, Italy, United Kingdom, Spain, Belgium, Austria and the Netherlands. Approximately 300 adult patients (≥18 years) from a mix of academic and non-academic sites (up to 65 sites) will be enrolled.

Official Title
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A Retrospective Non Interventional Study on First Line Treatment for Patients With BRAFV600E Mutant Metastatic Colorectal Cancer (mCRC)

Conditions
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BRAF V600E Mutation Positive, Metastatic Colorectal Cancer

Intervention / Treatment
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* Other: Non Interventional study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of histologically or cytologically confirmed CRC that is metastatic and unresectable Presence of BRAFV600E mutation in tumor tissue, as confirmed by a local assay Initiated first-line treatment with drugs registered for mCRC in the respective country at the time of treatment between January 1st, 2016 and December 31st, 2018 (both days inclusive) Provision of informed consent or non-opposition to the patient (or next of kin, if applicable) for the use of data, according to local regulations Exclusion Criteria: Patients will be excluded from the study if they fulfil any of the following criteria: Patients with another concomitant cancer at the time of diagnosis* Patients participating in interventional trials on investigational drugs at the time of initiation of first-line treatment Except for non-metastatic non-melanoma skin cancers, or in situ or benign neoplasms; a cancer will be considered concomitant if it occurs within 5 years of mCRC diagnosis.

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 |
| --- | --- |
| Non interventional<br>All BRAFV600E mutant patients having initiated a first-line treatment for mCRC between 01 January, 2016 and 31 December, 2018 (both days inclusive) with drugs registered for mCRC in respective country | Other: Non Interventional study<br>* Non Interventional study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First-line Systemic anticancer therapy (SACT) treatment patterns in BRAFV600E mutant mCRC patients | Agent or combination of agents received, Duration of treatment, Maintenance therapy (if any) | time of treatment initiation (for mCRC) until the time of first documented disease progression, treatment discontinuation or switch, whichever is earlier or end of study observation period up to 31 December 2020 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demographic and clinical characteristics | Description of the demographic and clinical profile of patients at the time of treatment initiation (for mCRC) | from the date of the start of first-line treatment for mCRC until the end of the observation period (date of death or last day of study observation period for patients alive at the time of data abstraction) up to 31 December 2020 | 
| Progression-free Survival (PFS) | the length of time between initiation of first-line treatment for mCRC and the first documented disease progression | from the date of the start of first-line treatment for mCRC until the end of the observation period (date of death or last day of study observation period for patients alive at the time of data abstraction) up to 31 December 2020 | 
| Overall Survival (OS) | length of time between first-line treatment initiation (for mCRC) and death (due to any cause) | from the date of the start of first-line treatment for mCRC until the end of the observation period (date of death or last day of study observation period for patients alive at the time of data abstraction) up to 31 December 2020 | 
| Overall Response rate (ORR) | number of complete response (CR) or partial response (PR) | from the date of the start of first-line treatment for mCRC until the end of first-line treatment up to 31 December 2020 | 
| Time to treatment cessation | the length of time between initiation of first-line treatment for mCRC and documented disease progression (or start of subsequent Line Of Treatment (LOT), if disease progression is not well documented in patient medical record), treatment discontinuation or switch to another treatment (defined as change from one treatment regimen to another treatment regimen, e.g., change from FOLFOX-based regimen to FOLFIRI or irinotecan-based regimen) | from the date of the start of first-line treatment for mCRC until the documented disease progression up to 31 December 2020 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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first line, retrospective study, mCRC, BRAF V600E