Treatment Patterns and Outcomes of Targeted Therapy and Immunotherapy Among BRAF-Positive Melanoma Patients Treated in the Adjuvant Setting and Among BRAF-Positive Metastatic Melanoma Patients With Low Tumor Burden

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT05611229

Collaborator

(none)

1,975

Enrollment

Location

17.6

Actual Duration (Months)

112.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This was an observational study utilizing electronic health record (EHR)-derived data collected retrospectively during routine care of real-world patients with advanced melanoma from NOBLE (Novartis Braf+ meLanoma patients ObsErvational) dataset.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Melanoma	Drug: Nivolumab Drug: Pembrolizumab Combination Product: Dabrafenib+Trametinib Combination Product: Ipilimumab+Nivolumab Combination Product: Vemurafenib+Cobimetinib Combination Product: Encorafenib+Binimetinib

Detailed Description

The NOBLE database was built from the harmonization of two customized oncology specific EHR databases: Flatiron Health Spotlight and Concerto Custom Patient360. BRAF v600 mutated advanced (i.e., stage III or IV) patients treated at oncology practices across the US were identified in these two databases for potential inclusion. Both the Flatiron Health EHR-derived database and the Concerto Patient360 database contain clinical, demographic, treatment, and mortality information for melanoma patients from the time of initial diagnosis until death or the most recent data cut-off, which is August 31, 2020 (for population 1), and May 31, 2020 (for population 2).

For population 1 (patients treated in the adjuvant setting): included patients were aged more than or equal to 18 years, were required to have a diagnosis of melanoma (ICD-9 172.x & ICD-10 C43.x or D03.x), pathologic stage III disease, evidence of resection, adjuvant treatment with Immunotherapy (IO) (e.g., Nivolumab (nivo) or Pembrolizumab (pembro)) or Targeted Therapy (TT) (e.g., Dabrafenib+ Trametinib (dab+tram)) on or after January 1, 2014 and prior to August 30,2020 (data cut-off), and any evidence of a BRAF+ result. Patients were required to have at least 6 months of follow-up after initiation of adjuvant treatment. Patients were followed until the earlier of death, data cut-off, loss of follow-up, or received MM diagnosis. While the first systemic therapy approved for use in the adjuvant melanoma setting occurred in 2015, the study period of interest begins on January 1, 2014, to include any potential off-label use of these therapies as adjuvant therapies.

For population 2 (patients with Low tumor burden (LTB) treated in the metastatic setting):

included patients were aged more than or equal to 18 years, and were required to have a diagnosis of melanoma (ICD-9 172.x & ICD-10 C43 or D03x), a pathologic stage IV diagnosis, treatment with IO (e.g. Ipilimumab (ipi), nivo, pembro, ipi+nivo) or TT (dab+tram, Vemurafenib+Cobimetinib, Encorafenib+Binimetinib (vem+cobi, enco+bini) on or after January 1, 2014 and prior to May 31, 2020 (data cut-off), and evidence of a BRAF+ result after therapy initiation. Patients were required to be classified as LTB at the time of stage IV diagnosis. LTB was defined as having normal LDH and <3 metastatic sites at the time of stage IV diagnosis. To align with recent FDA approvals for combination therapies use in the MM setting, the study period of interest began on January 1, 2014. Furthermore, this sampling interval allowed for a maximum of 6 years of follow-up from the start of study period.

Study Design

Study Type:

Observational

Actual Enrollment :

1975 participants

Observational Model:

Cohort

Time Perspective:

Retrospective

Official Title:

Real-World Treatment Patterns and Outcomes of Targeted Therapy and Immunotherapy Among BRAF-Positive Melanoma Patients Treated in the Adjuvant Setting and Among BRAF-Positive Metastatic Melanoma Patients With Low Tumor Burden: An Observational Study

Actual Study Start Date :

Jun 16, 2020

Actual Primary Completion Date :

Dec 3, 2021

Actual Study Completion Date :

Dec 3, 2021

Arms and Interventions

Arm	Intervention/Treatment
Population 1: BRAF+ melanoma patients treated with either TT or IO in the adjuvant setting Included patients were aged more than or equal to 18 years, were required to have a diagnosis of melanoma (ICD-9 172.x & ICD-10 C43.x or D03.x), pathologic stage III disease, evidence of resection, adjuvant treatment with IO (e.g., nivo or pembro) or TT (e.g., dab+tram) on or after January 1, 2014, and prior to August 30,2020 (data cut-off), and any evidence of a BRAF+ result.	Drug: Nivolumab Nivolumab Drug: Pembrolizumab Pembrolizumab Combination Product: Dabrafenib+Trametinib Dabrafenib+Trametinib
Population 2: BRAF+ melanoma patients with LTB treated with TT or IO in the metastatic setting Included patients were aged more than or equal to 18 years, and were required to have a diagnosis of melanoma (ICD-9 172.x & ICD-10 C43 or D03x), a pathologic stage IV diagnosis, treatment with IO (e.g. ipi, nivo, pembro, ipi+nivo) or TT (dab+tram, vem+cobi, enco+bini) on or after January 1, 2014 and prior to May 31, 2020 (data cut-off), and evidence of a BRAF+ result after therapy initiation. Patients were required to be classified as LTB at the time of stage IV diagnosis. LTB was defined as having normal LDH and <3 metastatic sites at the time of stage IV diagnosis.	Drug: Nivolumab Nivolumab Drug: Pembrolizumab Pembrolizumab Combination Product: Dabrafenib+Trametinib Dabrafenib+Trametinib Combination Product: Ipilimumab+Nivolumab Ipilimumab+Nivolumab Combination Product: Vemurafenib+Cobimetinib Vemurafenib+Cobimetinib Combination Product: Encorafenib+Binimetinib Encorafenib+Binimetinib

Arm

Intervention/Treatment

Population 1: BRAF+ melanoma patients treated with either TT or IO in the adjuvant setting

Included patients were aged more than or equal to 18 years, were required to have a diagnosis of melanoma (ICD-9 172.x & ICD-10 C43.x or D03.x), pathologic stage III disease, evidence of resection, adjuvant treatment with IO (e.g., nivo or pembro) or TT (e.g., dab+tram) on or after January 1, 2014, and prior to August 30,2020 (data cut-off), and any evidence of a BRAF+ result.

Drug: Nivolumab

Nivolumab

Drug: Pembrolizumab

Pembrolizumab

Combination Product: Dabrafenib+Trametinib

Dabrafenib+Trametinib

Population 2: BRAF+ melanoma patients with LTB treated with TT or IO in the metastatic setting

Included patients were aged more than or equal to 18 years, and were required to have a diagnosis of melanoma (ICD-9 172.x & ICD-10 C43 or D03x), a pathologic stage IV diagnosis, treatment with IO (e.g. ipi, nivo, pembro, ipi+nivo) or TT (dab+tram, vem+cobi, enco+bini) on or after January 1, 2014 and prior to May 31, 2020 (data cut-off), and evidence of a BRAF+ result after therapy initiation. Patients were required to be classified as LTB at the time of stage IV diagnosis. LTB was defined as having normal LDH and <3 metastatic sites at the time of stage IV diagnosis.

Drug: Nivolumab

Nivolumab

Drug: Pembrolizumab

Pembrolizumab

Combination Product: Dabrafenib+Trametinib

Dabrafenib+Trametinib

Combination Product: Ipilimumab+Nivolumab

Ipilimumab+Nivolumab

Combination Product: Vemurafenib+Cobimetinib

Vemurafenib+Cobimetinib

Combination Product: Encorafenib+Binimetinib

Encorafenib+Binimetinib

Outcome Measures

Primary Outcome Measures

Proportion of patients receiving TT and IO therapy in the first-, and second-line [throughout the study period, approximately 6 years (i.e., 01 January 2014 to 30 August 2020 for population 1 and 01 January 2014 to 31 May 2020 for population 2]
To describe treatment patterns among patients prescribed with TT versus IO in both the populations.
Proportion of patients switching from TT 1L therapy to IO 2L therapy [throughout the study period, approximately 6 years (i.e., 01 January 2014 to 30 August 2020 for population 1 and 01 January 2014 to 31 May 2020 for population 2]
To describe treatment patterns among patients prescribed with TT versus IO in both the populations.
Proportion of patients switching from IO 1L therapy to TT 2L therapy [throughout the study period, approximately 6 years (i.e., 01 January 2014 to 30 August 2020 for population 1 and 01 January 2014 to 31 May 2020 for population 2]
To describe treatment patterns among patients prescribed with TT versus IO in both the populations.

Secondary Outcome Measures

Proportion of patients who discontinued treatment in 1L [throughout the study period, approximately 6 years (i.e., 01 January 2014 to 30 August 2020 for population 1 and 01 January 2014 to 31 May 2020 for population 2]
To evaluate discontinuation of 1L treatment among patients receiving TT or IO.
Reasons for discontinuation of treatment in 1L [throughout the study period, approximately 6 years (i.e., 01 January 2014 to 30 August 2020 for population 1 and 01 January 2014 to 31 May 2020 for population 2]
To evaluate discontinuation of 1L treatment among patients receiving TT or IO.
Time from initiation of 1L therapy to death for any reason [throughout the study period, approximately 6 years (i.e., 01 January 2014 to 30 August 2020 for population 1 and 01 January 2014 to 31 May 2020 for population 2]
To estimate OS from initiation of 1L treatment among patients receiving TT or IO.
Time from initiation of 1L therapy to recurrence (for population 1) [throughout the study period, approximately 6 years (i.e., 01 January 2014 to 30 August 2020)]
To estimate Recurrence Free Survival (RFS) (for population 1) from initiation of 1L treatment among patients receiving TT or IO.
Time from initiation of 1L therapy to progression or death (for population 2) [throughout the study period, approximately 6 years (i.e., 01 January 2014 to 31 May 2020)]
To estimate Progression Free Survival (PFS) (for population 2) from initiation of 1L treatment among patients receiving TT or IO.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Population 1(patients treated in the adjuvant setting)

Diagnosis of melanoma (ICD-9 172.x & ICD-10 C43.x or D03.x)
Pathologic stage III on or after 2011
Evidence of resection
Adjuvant treatment with IO (nivo, pembro) or TT (dab+tram) on or after 1/1/2014 and prior to 8/31/2020
At least 6 months of follow-up time (until death, end of data cut-off, loss-of-follow-up, or progressed to stage IV diagnosis) from the initiation of therapy
Evidence of a BRAF+ result ≤30 days after therapy initiation in the adjuvant setting
At least 18 years of age at the time of initiation of treatment
No documented receipt of a clinical trial treatment for cancer at any time on or after January 1, 2014

Population 2 (patients with LTB treated in the metastatic setting)

Diagnosis of melanoma (ICD-9 172.x & ICD-10 C43.x or D03.x)
Pathologic stage IV at initial diagnosis on or after 1/1/2011, or earlier stage disease accompanied by development of a first locoregional recurrence on or after 1/1/2011
1L treatment with IO (ipi, nivo, pembro, ipi+nivo) or TT (dab+tram, vemu+cobi, enco+bini) on or after 1/1/2014 and prior to 5/31/2020
At least 6 months of follow-up time (until death, loss of follow-up, or end of data cut-off) from the initiation of therapy
Evidence of a BRAF+ result ≤30 days after 1L therapy initiation
LTB, defined as having <3 involved organ sites and normal LDH test (less than upper limit of normal) at the time of receiving MM diagnosis
At least 18 years of age at the time of initiation of 1L treatment
No documented receipt of a clinical trial treatment for cancer at any time on or after 1/1/2014