Melanoma
Conditions
Keywords
BRAF-mutant, Metastatic melanoma
Brief summary
This study aims to compare real-world effectiveness of BRAF/MEK inhibitors in BRAF-mutant metastatic melanoma patients in the United States by line of therapy. The Flatiron Health electronic health record (EHR) data from US cancer clinics will be used for this retrospective database analysis.
Interventions
DRUGEncorafenib
450 mg QD
DRUGBinimetinib
45 mg BID
DRUGVemurafenib
960 mg BID for 28 days/cycle
DRUGCobimetinib
60 mg QD for 21 days/cycle
DRUGDabrafenib
150 mg BID
DRUGTrametinib
2 mg QD
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with melanoma based on International Classification of Disease 9th and 10th Revisions (ICD-9: 172.x; ICD-10: C43x, D03x) and ≥2 visits on different days in the Flatiron database on or after January 1, 2011. * Clinically confirmed diagnosis of melanoma with pathologic stages III or IV at initial diagnosis or earlier stage disease with a first locoregional or distant recurrence on or after January 1, 2011. * Age ≥18 years at the time of advanced melanoma diagnosis. * Evidence of ≥1 BRAF positive test result at any time based on laboratory or genetic analysis results.
Exclusion criteria
-• Patients with prior BRAF- or MEK-inhibitor therapy • Patients with ECOG performance status ≥ 2 (at the time of randomization for patients from COLUMBUS, during the baseline period for patients in Flatiron EHR)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | COLUMBUS: From date of randomization until death or censoring (approx 80.5 months); Flatiron: From index date until death due or censoring or end of follow-up period (92.7 months) | As per COLUMBUS trial, OS was defined as the time from the date of randomization to the date of death due to any cause; if death was not observed, participants were censored at the date of last contact or the data analysis cut-off date, whichever occurred first. As per Flatiron EHR, OS was defined as the time from the index date to the date of death; participants without a date of death were censored at their last known activity date or the end of the follow-up period, whichever occurred first. Index date in each treatment group was defined as the date of treatment initiation. Kaplan-Meier analyses was used for analysis. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | COLUMBUS: From date of randomization until death or censoring (approx 80.5 months); Flatiron: From index date until death due or censoring or end of follow-up period (92.7 months) | COLUMBUS:PFS=time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurred first; PD:at least 20 percentage (%) increase in the sum of diameter of all measured target lesions, reference to the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimiter square (mm2) or the appearance of 1 or more new lesion, if a participant did not have an event at the analysis cut-off date, PFS was censored at the date of the last adequate tumour assessment. Flatiron:PFS=time from the index date to either the date of first PD event or death in the absence of progression; participants without PD or death were censored at the last date the participant could have been assessed for progression or the data analysis cut-off date, whichever occurred first. Index date was =the date of treatment initiation. |
Countries
United States
Participant flow
Recruitment details
Data of eligible participants with v-Raf murine sarcoma viral oncogene homolog B protein (BRAF)V-600 mutant melanoma who aged greater than or equal to 18 years at the time of initiating treatment with encorafenib plus binimetinib (ENCO+BINI) or dabrafenib plus trametinib (DAB+TRAM) or vemurafenib plus cobimetinib (VEM+COBI) was collected retrospectively.
Pre-assignment details
Data sources: COLUMBUS trial from 30-Dec-2013-15-Sept-2020 \[approximately 80.5 months\] and Flatiron Health electronic health Records (EHR) real-world database (RWD) from duration of 09-Jan-2014-30-Sep-2021 \[92.7 months\]. Planned cohorts in this study: 1) ENCO+BINI, pooled across COLUMBUS and Flatiron EHR; 2) DAB+TRAM: from Flatiron EHR; 3) VEM+COBI: from Flatiron EHR. Available retrospective data was evaluated in this observational study from 17-Jan-2022-31-Dec-2023 (approximately 23.5 months).
Participants by arm
| Arm | Count |
|---|---|
| Encorafenib+Binimetinib Participants with BRAFV600-mutant metastatic melanoma, who were enrolled between 30-December 2013 to 15-September-2020 in phase 3 COLUMBUS trial and eligible participants from RWD cohort identified from Flatiron Health Database between 27-June-2018 to 30-September- 2021 and treated with Encorafenib 450 mg QD and Binimetinib 45 mg BID (ENCO+BINI) were included. | 275 |
| Dabrafenib+Trametinib Eligible participants from RWD cohort with BRAFV600-mutant metastatic melanoma identified from Flatiron Health Database between 09-January-2014 to 30-September-2021 and treated with Dabrafenib 150 mg BID+ Trametinib 2 mg QD (DAB+TRAM) were included. | 387 |
| Vemurafenib + Cobimetinib Eligible participants from RWD cohort with BRAFV600-mutant metastatic melanoma identified from Flatiron Health Database between 10-November-2015 to 30-September-2021 and treated with Vemurafenib 960 mg BID+ Cobimetinib 60 mg QD (VEM+COBI) were included. | 54 |
| Total | 716 |
Baseline characteristics
| Characteristic | Encorafenib+Binimetinib | Dabrafenib+Trametinib | Vemurafenib + Cobimetinib | Total |
|---|---|---|---|---|
| Age, Continuous | 57.5 Years STANDARD_DEVIATION 13.9 | 59.3 Years STANDARD_DEVIATION 13.5 | 56.4 Years STANDARD_DEVIATION 14.6 | 58.4 Years STANDARD_DEVIATION 13.7 |
| Race/Ethnicity, Customized Non-white | 22 Participants | 34 Participants | 6 Participants | 62 Participants |
| Race/Ethnicity, Customized White | 253 Participants | 353 Participants | 48 Participants | 654 Participants |
| Sex: Female, Male Female | 113 Participants | 151 Participants | 17 Participants | 281 Participants |
| Sex: Female, Male Male | 162 Participants | 236 Participants | 37 Participants | 435 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 159 / 275 | 259 / 387 | 30 / 54 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Overall Survival (OS)
As per COLUMBUS trial, OS was defined as the time from the date of randomization to the date of death due to any cause; if death was not observed, participants were censored at the date of last contact or the data analysis cut-off date, whichever occurred first. As per Flatiron EHR, OS was defined as the time from the index date to the date of death; participants without a date of death were censored at their last known activity date or the end of the follow-up period, whichever occurred first. Index date in each treatment group was defined as the date of treatment initiation. Kaplan-Meier analyses was used for analysis.
Time frame: COLUMBUS: From date of randomization until death or censoring (approx 80.5 months); Flatiron: From index date until death due or censoring or end of follow-up period (92.7 months)
Population: Analysis population included all eligible participants whose data were retrieved and observed in this study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dabrafenib+Trametinib | Overall Survival (OS) | 16.1 Months |
| Vemurafenib + Cobimetinib | Overall Survival (OS) | 25.0 Months |
| Encorafenib+Binimetinib | Overall Survival (OS) | 30.0 Months |
Comparison: Statistical analysis data is presented for Dabrafenib+Trametinib relative to Encorafenib+Binimetinib (reference).p-value: 0.0295% CI: [1.05, 1.65]Wald Chi- Square Statistic
Comparison: Statistical analysis data is presented for Vemurafenib + Cobimetinib relative to Encorafenib+Binimetinib (reference).p-value: 0.4795% CI: [0.76, 1.79]Wald Chi- Square Statistic
Other Pre-specified
Progression Free Survival (PFS)
COLUMBUS:PFS=time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurred first; PD:at least 20 percentage (%) increase in the sum of diameter of all measured target lesions, reference to the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimiter square (mm2) or the appearance of 1 or more new lesion, if a participant did not have an event at the analysis cut-off date, PFS was censored at the date of the last adequate tumour assessment. Flatiron:PFS=time from the index date to either the date of first PD event or death in the absence of progression; participants without PD or death were censored at the last date the participant could have been assessed for progression or the data analysis cut-off date, whichever occurred first. Index date was =the date of treatment initiation.
Time frame: COLUMBUS: From date of randomization until death or censoring (approx 80.5 months); Flatiron: From index date until death due or censoring or end of follow-up period (92.7 months)
Population: Analysis population included all eligible participants whose data were retrieved and observed in this study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dabrafenib+Trametinib | Progression Free Survival (PFS) | 7.4 Months |
| Vemurafenib + Cobimetinib | Progression Free Survival (PFS) | 7.9 Months |
| Encorafenib+Binimetinib | Progression Free Survival (PFS) | 14.1 Months |
Comparison: Statistical analysis data is presented for Dabrafenib+Trametinib relative to Encorafenib+Binimetinib (reference).p-value: <0.00195% CI: [1.2, 1.87]Wald Chi- Square Statistic
Comparison: Statistical analysis data is presented for Vemurafenib + Cobimetinib relative to Encorafenib+Binimetinib (reference).p-value: 0.495% CI: [0.79, 1.82]Wald Chi- Square Statistic