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

Completed

• Conditions: Metastatic Melanoma
• Interventions: Drug: Nivolumab; Drug: Pembrolizumab; Combination Product: Dabrafenib+Trametinib; Combination Product: Ipilimumab+Nivolumab; Combination Product: Vemurafenib+Cobimetinib; Combination Product: Encorafenib+Binimetinib

• Registration Number: NCT05611229
• Lead Sponsor: Novartis Pharmaceuticals

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.

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 Timeline

• Study Start: 2020-06-16
• Primary Completion: 2021-12-03
• Study Completion: 2021-12-03
• Study First Submitted: 2022-11-04
• Study First Submitted QC: 2022-11-04
• Study First Posted: 2022-11-09
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-05
• Last Update Posted: 2023-04-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1975

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

Exclusion Criteria

None

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Population 1: BRAF+ melanoma patients treated with either TT or IO in the adjuvant setting	Dabrafenib+Trametinib	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.
Population 2: BRAF+ melanoma patients with LTB treated with TT or IO in the metastatic setting	Ipilimumab+Nivolumab	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.
Population 2: BRAF+ melanoma patients with LTB treated with TT or IO in the metastatic setting	Dabrafenib+Trametinib	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.
Population 2: BRAF+ melanoma patients with LTB treated with TT or IO in the metastatic setting	Vemurafenib+Cobimetinib	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.
Population 2: BRAF+ melanoma patients with LTB treated with TT or IO in the metastatic setting	Encorafenib+Binimetinib	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.
Population 1: BRAF+ melanoma patients treated with either TT or IO in the adjuvant setting	Nivolumab	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.
Population 1: BRAF+ melanoma patients treated with either TT or IO in the adjuvant setting	Pembrolizumab	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.
Population 2: BRAF+ melanoma patients with LTB treated with TT or IO in the metastatic setting	Nivolumab	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.
Population 2: BRAF+ melanoma patients with LTB treated with TT or IO in the metastatic setting	Pembrolizumab	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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 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.
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.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇺🇸 East Hanover, New Jersey, United States