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BRAF genotypes exhibit different clinical, pathologic profiles

NEW YORK — An analysis of the clinical and pathologic profiles of BRAF genotypes among individuals with melanoma revealed differences related to patient age at presentation, recurrence rates and disease-specific mortality, according to study results presented at HemOnc Today Melanoma and Cutaneous Malignancies.

Patients with BRAF V600K mutations experienced the highest recurrence rates, and all recurrences in this group were metastatic. However, they were less likely to die of melanoma, possibly due to older age at presentation and death from other comorbidities.

BRAF mutations are present in approximately half of malignant melanomas, and their identification has revolutionized treatment of advanced disease. Nearly 300 distinct missense mutations have been identified in 115 of the 766 BRAF amino acids.

Neha Goel, surgical oncology fellow at Fox Chase Cancer Center, and colleagues used molecular profiling to analyze the clinical and pathologic profiles of patients with four BRAF genotypes: G466V, V600E, V600R and V600K.

They analyzed 162 patients, 50 (31%) of whom harbored BRAF mutations. All but one of these patients was white, and 62% were men.

Median age at presentation was 56 years for those with V600E genotype (n – 34), 67 years for those with V600K genotype (n = 9), 62 years for those with V600R genotype (n =4) and 66 years for those with G466V genotype (n = 3).

Researchers reported median Breslow thickness depths of 2.13 mm for patients with V600E mutations, 2.5 mm for those with V600K mutations, 1.9 mm for those with V600R mutations and 5 mm for those with G466V mutations.

The majority of patients with V600E, V600K and G466 genotypes had stage II disease, whereas most of those with V600R genotype had stage III disease.

Patients with V600K genotypes had the highest recurrence rates (44%), followed by V600E (38%) and V600R (25%). All recurrences among those with V600K and V600R genotypes were metastatic, compared with 69% of recurrences among those with V600E genotypes.

No patients with G466V genotypes experienced disease recurrence.

Researchers reported melanoma mortality rates of 11% among those with V600E mutations, 22% among those with V600K mutations, 50% among those with V600R mutations and 33% among those with G466V mutations.

Patients with V600E genotypes achieved the longest median DFS (72 months), followed by those with V600K (17.6), V600R (11.3 months) and G466V (5.8 months).

Patients with V600E genotypes also achieved the longest median OS (not reached), followed by V600K (18.6 months), V600R (11.7 months) and G466V (8.8 months).

“Further studies will examine these genotypes to evaluate trends that may lead to more effective individualized treatment plans,” Goel and colleagues wrote. – by Mark Leiser

Reference:

Goel N, et al. Clinical and pathologic profiles of BRAF genotypes. Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; March 24-25, 2017; New York.

Disclosure: HemOnc Today could not confirm the researchers’ relevant financial disclosures at the time of reporting.

NEW YORK — An analysis of the clinical and pathologic profiles of BRAF genotypes among individuals with melanoma revealed differences related to patient age at presentation, recurrence rates and disease-specific mortality, according to study results presented at HemOnc Today Melanoma and Cutaneous Malignancies.

Patients with BRAF V600K mutations experienced the highest recurrence rates, and all recurrences in this group were metastatic. However, they were less likely to die of melanoma, possibly due to older age at presentation and death from other comorbidities.

BRAF mutations are present in approximately half of malignant melanomas, and their identification has revolutionized treatment of advanced disease. Nearly 300 distinct missense mutations have been identified in 115 of the 766 BRAF amino acids.

Neha Goel, surgical oncology fellow at Fox Chase Cancer Center, and colleagues used molecular profiling to analyze the clinical and pathologic profiles of patients with four BRAF genotypes: G466V, V600E, V600R and V600K.

They analyzed 162 patients, 50 (31%) of whom harbored BRAF mutations. All but one of these patients was white, and 62% were men.

Median age at presentation was 56 years for those with V600E genotype (n – 34), 67 years for those with V600K genotype (n = 9), 62 years for those with V600R genotype (n =4) and 66 years for those with G466V genotype (n = 3).

Researchers reported median Breslow thickness depths of 2.13 mm for patients with V600E mutations, 2.5 mm for those with V600K mutations, 1.9 mm for those with V600R mutations and 5 mm for those with G466V mutations.

The majority of patients with V600E, V600K and G466 genotypes had stage II disease, whereas most of those with V600R genotype had stage III disease.

Patients with V600K genotypes had the highest recurrence rates (44%), followed by V600E (38%) and V600R (25%). All recurrences among those with V600K and V600R genotypes were metastatic, compared with 69% of recurrences among those with V600E genotypes.

No patients with G466V genotypes experienced disease recurrence.

Researchers reported melanoma mortality rates of 11% among those with V600E mutations, 22% among those with V600K mutations, 50% among those with V600R mutations and 33% among those with G466V mutations.

Patients with V600E genotypes achieved the longest median DFS (72 months), followed by those with V600K (17.6), V600R (11.3 months) and G466V (5.8 months).

Patients with V600E genotypes also achieved the longest median OS (not reached), followed by V600K (18.6 months), V600R (11.7 months) and G466V (8.8 months).

“Further studies will examine these genotypes to evaluate trends that may lead to more effective individualized treatment plans,” Goel and colleagues wrote. – by Mark Leiser

Reference:

Goel N, et al. Clinical and pathologic profiles of BRAF genotypes. Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; March 24-25, 2017; New York.

Disclosure: HemOnc Today could not confirm the researchers’ relevant financial disclosures at the time of reporting.

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