Metastatic Cancers
Conditions
Keywords
V600 BRAF mutation, Metastatic melanoma
Brief summary
This is a national, multicenter, cross-sectional epidemiological study in adult Spanish participants diagnosed with advanced or metastatic melanoma.
Interventions
None listed
Sponsors
Hoffmann-La Roche
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Valid tumor samples from participants diagnosed with Stage IIIc or IV melanoma * Written informed consent granted
Exclusion criteria
\- Do not fulfill one or more inclusion criteria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With V600 BRAF Mutation Status | Day 1 | Presence or absence of mutations in the V600 BRAF oncogene was determined in all eligible participants. Data collection and management of BRAF mutation testing was carried out using the Biomarker point® online platform. The platform was used as an electronic case report form (e-CRF) for collecting information in electronic format via a website. Percentage of participants with BRAF mutation status (mutated BRAF, wild type, not available) were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Family History of Melanoma | Day 1 | — |
| Percentage of Participants With Sun Exposure | Day 1 | Data were obtained to classify the population with sun exposure as those with low, intermittent or chronic exposure. For the sub-analysis of low, intermittent and chronic exposure, percentages were calculated based on the population with any sun exposure. |
| Percentage of Participants Categorized by Primary Tumor Location | Day 1 | Primary tumor location included limbs (upper and lower extremities), trunk, head/neck, mucosa, uveal, acral, other (other than these specified locations), unknown (exact location unknown), and not available. |
| Percentage of Participants Categorized By LDH Level | Day 1 | Normal LDH levels range from 140 units per liter (U/L) to 280 U/L. |
| Median Time Since Diagnosis of Melanoma | Day 1 | Median time from the diagnosis of primary melanoma to advanced disease was determined in years. |
| Percentage of Participants Categorized by Tumor Sample Source (Primary Tumor or Metastatic Sites) | Day 1 | — |
| Percentage of Participants Categorized by Tumor Sample Type (Paraffin-embedded Tissue Blocks, Paraffin Block Slides, Cytology Slides, or Other) | Day 1 | — |
| Percentage of Participants Categorized by Method of Fixation (Buffered Formalin or Others) | Day 1 | — |
| Percentage of Participants Categorized by Melanoma Stage | Day 1 | Melanoma stages were categorized (according to American Joint Committee on Cancer \[AJCC\]) as IIIc (advanced stage of melanoma), M1a (metastases to skin, subcutaneous, or distant lymph nodes, normal lactate dehydrogenase (LDH) level, M1b (lung metastases, normal LDH) and M1c (metastases to all other visceral sites and normal LDH or distant metastases to any site combined with an elevated serum LDH level). Of these Stage IIIc was used as the referral category for comparisons. |
| Percentage of Participants With Ulceration | Day 1 | — |
| Percentage of Participants With Regression | Day 1 | Regression in melanoma is the replacement of tumor tissue with fibrosis, degenerated melanoma cells, lymphocytic proliferation, and telangiectasia formation. |
| Percentage of Participants With Vascular Invasion | Day 1 | Vascular invasion is defined as the appearance of cancer cells in the lymphatic and blood streams. |
| Percentage of Participants Categorized by Method of DNA Extraction (Cobas® BRAF V600 Mutation Test or Others) | Day 1 | — |
| Percentage of Participants Categorized by Method of BRAF Mutation Testing (Cobas® 4800 BRAF V600 Mutation Test or Others) | Day 1 | — |
| Percentage Participants Categorized by the Percentage of Tumor Cells Referred to the Technique | Day 1 | The samples were classified based on the percentage of tumor cells referred to the technique as follows: \<60 percent (%), 60-80%, \>80% and Unknown. |
| Percentage of Participants With Adequate Quality/Quantity of Tumor Sample | Day 1 | — |
| Percentage of Participants Categorized by Breslow Thickness | Day 1 | Breslow thickness is defined as the total vertical height of the melanoma, from the very top (called the granular layer) to the area of deepest penetration in the skin. An instrument called an ocular micrometer is used to measure the thickness of the excised (removed) tumor. In general, the higher the Breslow thickness, the worse the prognosis. The classifications were lesser than or equal to (≤) 1.0 millimeters (mm), 1.01 - 2.0 mm, 2.01 - 4.0 mm, greater than (\>) 4.0 mm and Unknown. |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metastatic Melanoma Participants with metastatic melanoma who attended their physicians during the 18-month recruitment period and had valid biological samples available for BRAF mutation testing were included in the study. There was no intervention in this study. | 264 |
| Total | 264 |
Baseline characteristics
| Characteristic | Metastatic Melanoma |
|---|---|
| Age, Continuous | 68.0 years |
| Sex: Female, Male Female | 113 Participants |
| Sex: Female, Male Male | 151 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Percentage of Participants With V600 BRAF Mutation Status
Presence or absence of mutations in the V600 BRAF oncogene was determined in all eligible participants. Data collection and management of BRAF mutation testing was carried out using the Biomarker point® online platform. The platform was used as an electronic case report form (e-CRF) for collecting information in electronic format via a website. Percentage of participants with BRAF mutation status (mutated BRAF, wild type, not available) were reported.
Time frame: Day 1
Population: All enrolled participants were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Melanoma | Percentage of Participants With V600 BRAF Mutation Status | Mutated BRAF | 41.3 percentage of participants |
| Metastatic Melanoma | Percentage of Participants With V600 BRAF Mutation Status | Wild type | 58.3 percentage of participants |
| Metastatic Melanoma | Percentage of Participants With V600 BRAF Mutation Status | Not available | 0.4 percentage of participants |
Secondary
Median Time Since Diagnosis of Melanoma
Median time from the diagnosis of primary melanoma to advanced disease was determined in years.
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis except for one participant with missing data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Metastatic Melanoma | Median Time Since Diagnosis of Melanoma | 1.0 years |
Comparison: The association of time since diagnosis of primary melanoma (continuous variable) with the risk of BRAF mutation (Yes/No) was assessed using bivariate regression analysis.p-value: 0.291Bivariate regression analysis
Secondary
Percentage of Participants Categorized by Breslow Thickness
Breslow thickness is defined as the total vertical height of the melanoma, from the very top (called the granular layer) to the area of deepest penetration in the skin. An instrument called an ocular micrometer is used to measure the thickness of the excised (removed) tumor. In general, the higher the Breslow thickness, the worse the prognosis. The classifications were lesser than or equal to (≤) 1.0 millimeters (mm), 1.01 - 2.0 mm, 2.01 - 4.0 mm, greater than (\>) 4.0 mm and Unknown.
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Melanoma | Percentage of Participants Categorized by Breslow Thickness | ≤1 mm | 5.7 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Breslow Thickness | 1.01 - 2.0 mm | 14.4 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Breslow Thickness | 2.01 - 4.0 mm | 22.3 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Breslow Thickness | >4 mm | 27.3 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Breslow Thickness | Unknown | 30.3 percentage of participants |
Comparison: The association of Berslow thickness (≤1 mm \[referral category\] vs 1.01-2 mm vs 2.01-4 mm vs 4 mm) with the risk of BRAF mutation (Yes/No) was assessed using bivariate regression analysis.p-value: 0.683Bivariate regression analysis
Secondary
Percentage of Participants Categorized By LDH Level
Normal LDH levels range from 140 units per liter (U/L) to 280 U/L.
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Melanoma | Percentage of Participants Categorized By LDH Level | Normal | 20.1 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized By LDH Level | High | 51.5 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized By LDH Level | Unknown | 28.4 percentage of participants |
Comparison: The association of LDH (elevated \[referral category\] vs normal vs unknown) with the risk of BRAF mutation (Yes/No) was assessed using bivariate regression analysis.p-value: 0.313Bivariate regression analysis
Secondary
Percentage of Participants Categorized by Melanoma Stage
Melanoma stages were categorized (according to American Joint Committee on Cancer \[AJCC\]) as IIIc (advanced stage of melanoma), M1a (metastases to skin, subcutaneous, or distant lymph nodes, normal lactate dehydrogenase (LDH) level, M1b (lung metastases, normal LDH) and M1c (metastases to all other visceral sites and normal LDH or distant metastases to any site combined with an elevated serum LDH level). Of these Stage IIIc was used as the referral category for comparisons.
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Melanoma | Percentage of Participants Categorized by Melanoma Stage | IIIc | 14.4 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Melanoma Stage | M1a | 19.3 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Melanoma Stage | M1b | 13.3 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Melanoma Stage | M1c | 22.7 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Melanoma Stage | Missing data | 29.9 percentage of participants |
Comparison: The association of Melanoma Stage (IIIC \[referral category\] versus (vs) M1a vs M1b vs M1c) with the risk of BRAF mutation (Yes/No) was assessed using bivariate regression analysis.p-value: 0.001Bivariate regression analysis
Comparison: The association of Melanoma Stage IIIC/M1a/M1b \[referral category\] vs M1c with the risk of BRAF mutation (Yes/No) was assessed using bivariate regression analysis.p-value: 0.196Bivariate regression analysis
Comparison: The association of Melanoma Stage IIIc with the risk of BRAF mutation (Yes/No) was assessed using multivariate regression analysis.p-value: 0.002Multivariate regression analysis
Comparison: The association of Melanoma Stage M1a (using Melanoma Stage IIIC as referral category) with the risk of BRAF mutation (Yes/No) was assessed using multivariate regression analysis.p-value: 0.02895% CI: [1.115, 6.616]Multivariate regression analysis
Comparison: The association of Melanoma Stage M1b (using Melanoma Stage IIIC as referral category) with the risk of BRAF mutation (Yes/No) was assessed using multivariate regression analysis.p-value: 0.14295% CI: [0.168, 1.291]Multivariate regression analysis
Comparison: The association of Melanoma Stage M1c (using Melanoma Stage IIIC as referral category) with the risk of BRAF mutation (Yes/No) was assessed using multivariate regression analysis.p-value: 0.65395% CI: [0.351, 1.928]Multivariate regression analysis
Secondary
Percentage of Participants Categorized by Method of BRAF Mutation Testing (Cobas® 4800 BRAF V600 Mutation Test or Others)
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Melanoma | Percentage of Participants Categorized by Method of BRAF Mutation Testing (Cobas® 4800 BRAF V600 Mutation Test or Others) | Cobas® 4800 BRAF V600 Mutation Test | 96.2 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Method of BRAF Mutation Testing (Cobas® 4800 BRAF V600 Mutation Test or Others) | Other | 3.8 percentage of participants |
Secondary
Percentage of Participants Categorized by Method of DNA Extraction (Cobas® BRAF V600 Mutation Test or Others)
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Melanoma | Percentage of Participants Categorized by Method of DNA Extraction (Cobas® BRAF V600 Mutation Test or Others) | Cobas® BRAF V600 Mutation Test | 93.1 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Method of DNA Extraction (Cobas® BRAF V600 Mutation Test or Others) | Other | 6.8 percentage of participants |
Secondary
Percentage of Participants Categorized by Method of Fixation (Buffered Formalin or Others)
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Melanoma | Percentage of Participants Categorized by Method of Fixation (Buffered Formalin or Others) | Buffered formalin | 92.8 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Method of Fixation (Buffered Formalin or Others) | Other | 5.3 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Method of Fixation (Buffered Formalin or Others) | Unknown | 1.9 percentage of participants |
Comparison: The association of method of fixation (buffered formalin \[referral category\] vs other) with the risk of BRAF mutation (Yes/No) was assessed using bivariate regression analysis.p-value: 0.701Bivariate regression analysis
Secondary
Percentage of Participants Categorized by Primary Tumor Location
Primary tumor location included limbs (upper and lower extremities), trunk, head/neck, mucosa, uveal, acral, other (other than these specified locations), unknown (exact location unknown), and not available.
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Melanoma | Percentage of Participants Categorized by Primary Tumor Location | Limbs (Upper extremities) | 9.1 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Primary Tumor Location | Limbs (Lower extremities) | 22.0 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Primary Tumor Location | Trunk | 28.4 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Primary Tumor Location | Head/Neck | 14.4 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Primary Tumor Location | Mucosa | 6.8 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Primary Tumor Location | Uveal | 4.2 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Primary Tumor Location | Acral | 1.1 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Primary Tumor Location | Other | 0.4 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Primary Tumor Location | Unknown | 8.7 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Primary Tumor Location | Not available | 6.1 percentage of participants |
Comparison: The association of primary tumor site (trunk \[referral category\] vs head and neck vs upper extremities vs lower extremities vs. visceral/mucosa) with the risk of BRAF mutation (Yes/No) was assessed using bivariate regression analysis.p-value: 0.262Bivariate regression analysis
Secondary
Percentage of Participants Categorized by Tumor Sample Source (Primary Tumor or Metastatic Sites)
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Melanoma | Percentage of Participants Categorized by Tumor Sample Source (Primary Tumor or Metastatic Sites) | Metastases | 62.9 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Tumor Sample Source (Primary Tumor or Metastatic Sites) | Primary tumor | 34.1 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Tumor Sample Source (Primary Tumor or Metastatic Sites) | Relapses | 2.3 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Tumor Sample Source (Primary Tumor or Metastatic Sites) | Unknown | 0.8 percentage of participants |
Comparison: The association of tumor sample source (primary tumor \[referral category\] vs metastases vs relapses) with the risk of BRAF mutation (Yes/No) was assessed using bivariate regression analysis.p-value: 0.164Bivariate regression analysis
Secondary
Percentage of Participants Categorized by Tumor Sample Type (Paraffin-embedded Tissue Blocks, Paraffin Block Slides, Cytology Slides, or Other)
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Melanoma | Percentage of Participants Categorized by Tumor Sample Type (Paraffin-embedded Tissue Blocks, Paraffin Block Slides, Cytology Slides, or Other) | Paraffin-embedded blocks | 73.5 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Tumor Sample Type (Paraffin-embedded Tissue Blocks, Paraffin Block Slides, Cytology Slides, or Other) | Slides of paraffin blocks | 22.3 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Tumor Sample Type (Paraffin-embedded Tissue Blocks, Paraffin Block Slides, Cytology Slides, or Other) | Cytological slides | 3.4 percentage of participants |
| Metastatic Melanoma | Percentage of Participants Categorized by Tumor Sample Type (Paraffin-embedded Tissue Blocks, Paraffin Block Slides, Cytology Slides, or Other) | Other | 0.8 percentage of participants |
Comparison: The association of tumor sample type (paraffin-embedded blocks \[referral category\] vs slides of paraffin blocks vs cytology slides) with the risk of BRAF mutation (Yes/No) was assessed using bivariate regression analysis.p-value: 0.505Bivariate regression analysis
Secondary
Percentage of Participants With Adequate Quality/Quantity of Tumor Sample
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metastatic Melanoma | Percentage of Participants With Adequate Quality/Quantity of Tumor Sample | 100.0 percentage of participants |
Secondary
Percentage of Participants With Family History of Melanoma
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Metastatic Melanoma | Percentage of Participants With Family History of Melanoma | 5.7 percentage of participants |
Comparison: The association of Family family history of melanoma (yes vs no) with the risk of BRAF mutation (Yes/No) was assessed using bivariate regression analysis.p-value: 0.24Bivariate regression analysis
Secondary
Percentage of Participants With Regression
Regression in melanoma is the replacement of tumor tissue with fibrosis, degenerated melanoma cells, lymphocytic proliferation, and telangiectasia formation.
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Melanoma | Percentage of Participants With Regression | With regression | 9.5 percentage of participants |
| Metastatic Melanoma | Percentage of Participants With Regression | Without regression | 53.0 percentage of participants |
| Metastatic Melanoma | Percentage of Participants With Regression | Unknown | 37.5 percentage of participants |
Comparison: The association of presence of regression (Without regression \[referral category\] vs With regression) with the risk of BRAF mutation (Yes/No) was assessed using bivariate regression analysis.p-value: 0.949Bivariate regression analysis
Secondary
Percentage of Participants With Sun Exposure
Data were obtained to classify the population with sun exposure as those with low, intermittent or chronic exposure. For the sub-analysis of low, intermittent and chronic exposure, percentages were calculated based on the population with any sun exposure.
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Melanoma | Percentage of Participants With Sun Exposure | Any exposure (n=264) | 49.2 percentage of participants |
| Metastatic Melanoma | Percentage of Participants With Sun Exposure | Low exposure (n=130) | 12.3 percentage of participants |
| Metastatic Melanoma | Percentage of Participants With Sun Exposure | Intermittent exposure (n=130) | 60.8 percentage of participants |
| Metastatic Melanoma | Percentage of Participants With Sun Exposure | Chronic exposure (n=130) | 26.9 percentage of participants |
| Metastatic Melanoma | Percentage of Participants With Sun Exposure | Missing data (n=264) | 13.6 percentage of participants |
Comparison: The association of sun exposure yes vs no with the risk of BRAF mutation (Yes/No) was assessed using bivariate regression analysis.p-value: 0.719Bivariate regression analysis
Secondary
Percentage of Participants With Ulceration
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Melanoma | Percentage of Participants With Ulceration | With ulceration | 41.7 percentage of participants |
| Metastatic Melanoma | Percentage of Participants With Ulceration | Without ulceration | 26.1 percentage of participants |
| Metastatic Melanoma | Percentage of Participants With Ulceration | Unknown | 32.2 percentage of participants |
Comparison: The association of Ulceration (no \[referral category\] vs yes) with the risk of BRAF mutation (Yes/No) was assessed using bivariate regression analysis.p-value: 0.615Bivariate regression analysis
Secondary
Percentage of Participants With Vascular Invasion
Vascular invasion is defined as the appearance of cancer cells in the lymphatic and blood streams.
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Melanoma | Percentage of Participants With Vascular Invasion | With vascular invasion | 8.3 percentage of participants |
| Metastatic Melanoma | Percentage of Participants With Vascular Invasion | Without vascular invasion | 58.7 percentage of participants |
| Metastatic Melanoma | Percentage of Participants With Vascular Invasion | Unknown | 33.0 percentage of participants |
Comparison: The association of Vascular invasion (Without vascular invasion \[referral category\] vs With vascular invasion) with the risk of BRAF mutation (Yes/No) was assessed using bivariate regression analysis.p-value: 0.374Bivariate regression analysis
Secondary
Percentage Participants Categorized by the Percentage of Tumor Cells Referred to the Technique
The samples were classified based on the percentage of tumor cells referred to the technique as follows: \<60 percent (%), 60-80%, \>80% and Unknown.
Time frame: Day 1
Population: All participants enrolled in the study were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Metastatic Melanoma | Percentage Participants Categorized by the Percentage of Tumor Cells Referred to the Technique | <60% | 12.1 percentage of participants |
| Metastatic Melanoma | Percentage Participants Categorized by the Percentage of Tumor Cells Referred to the Technique | 60-80% | 31.4 percentage of participants |
| Metastatic Melanoma | Percentage Participants Categorized by the Percentage of Tumor Cells Referred to the Technique | >80% | 33.0 percentage of participants |
| Metastatic Melanoma | Percentage Participants Categorized by the Percentage of Tumor Cells Referred to the Technique | Unknown | 23.5 percentage of participants |