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Pretreatment affects outcomes in patients with metastatic melanoma
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Prior treatment appeared to considerably affect how patients with stage IV metastatic melanoma responded to vemurafenib therapy, according to study results.
Those who had undergone prior treatment with immunotherapy demonstrated better outcomes with vemurafenib (Zelboraf, Hoffmann-La Roche) than those who underwent prior treatment with chemotherapy or kinase inhibitors, results showed.
“Kinase inhibitors targeting the BRAF V600 mutation have become standard in the treatment of metastatic melanoma,” Selma Ugurel, MD, of the department of dermatology at the University of Essen in Germany, and colleagues wrote. “Albeit in wide clinical use, the patterns associated with therapy outcome are not fully elucidated. The present study was aimed to identify predictive factors of therapy response and survival under the BRAF inhibitor vemurafenib.”
The multicenter, retrospective Dermatologic Cooperative Oncology Group study evaluated patient, tumor and pretreatment characteristics of individuals with BRAF V600-mutated stage IV melanoma prior to initiation of treatment with single-agent vemurafenib.
The analysis included 300 patients from 14 centers. Median follow-up was 13 months.
Researchers reported median PFS of 5.1 months and median OS of 7.6 months.
Ugurel and colleagues found that best response to vemurafenib was associated with serum level of lactate dehydrogenase [LDH (≤ vs. > upper normal limit; P=.0000001)], ECOG overall performance status (0 vs. ≥1; P=.00089), and BRAF mutation subtype (V600E vs. V600K; P=.016).
Independent predictors of PFS identified by multivariate analysis included ECOG overall performance status of ≥1 (HR=1.88; P=.00005), immunotherapy pretreatment (HR=0.53; P=.0067), elevated serum LDH (HR=1.45; P=.012), age >55 years (HR=0.72; P=.019), and chemotherapy pretreatment (HR=1.39; P=.036)
Predictors of OS included elevated serum LDH (HR=1.99; P=.00012), ECOG overall performance status ≥1 (HR=1.9; P=.00063), age >55 years (HR=0.65; P=.011), kinase inhibitor pretreatment (HR=1.86; P=.014), immunotherapy pretreatment (HR=0.57; P=.025), chemotherapy pretreatment (HR=2.17; P=.039) and male gender (HR=0.7; P=.039).
“Our data demonstrate that the type of pretreatment strongly influences the outcome of vemurafenib therapy, with a precedent immunotherapy showing a positive, and a prior chemotherapy and kinase inhibitors showing a negative impact on survival, respectively,” Ugurel and colleagues wrote. “Moreover, we show that the patient’s overall performance status, serum LDH, age and gender independently impact vemurafenib therapy outcome. These findings should be taken into account for future design of therapy sequencing in BRAF V600 mutation-positive melanoma patients.”
Disclosure: See the full study for a list of the researchers’ relevant financial disclosures.
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