Menzies Alexander M, Wilmott James S, Drummond Martin, Lo Serigne, Lyle Megan, Chan Matthew M K, Thompson John F, Guminski Alex, Carlino Matteo S, Scolyer Richard A, Kefford Richard F, Long Georgina V
Melanoma Institute Australia, Sydney, Australia.
The University of Sydney, Sydney, Australia.
Cancer. 2015 Nov 1;121(21):3826-35. doi: 10.1002/cncr.29586. Epub 2015 Jul 28.
The degree of response and the duration of survival of patients treated with mitogen-activated protein kinase (MAPK) inhibitors are highly variable. Whether baseline clinicopathologic factors can predict the clinical course with treatment is largely unknown.
For 142 consecutive immunotherapy- and MAPK inhibitor-naive patients with BRAF-mutant metastatic melanoma who were treated during clinical trials with BRAF inhibitors (n = 111) or a combination of dabrafenib and trametinib (n = 31), clinicopathologic factors were correlated with the response to MAPK inhibitors and survival.
The median follow-up was 15.7 months (range, 0.6-60.5 months). The 2-, 3-, and 4-year overall survival (OS) rates were 43%, 24%, and 24%, respectively. A multivariate analysis demonstrated that the only clinicopathologic factors associated with longer progression-free survival (PFS) and OS were female sex and a normal pretreatment serum lactate dehydrogenase (LDH) level. The BRAF V600E genotype and an absence of primary melanoma ulceration were also independently associated with longer PFS but not OS. The median OS was 23.5 months for patients with normal LDH levels and 7.3 months for those with elevated LDH levels (hazard ratio, 0.31; P < .001). Complete responders had the best survival, but disease progression still occurred in 2 of 7 patients.
Long-term survival occurs for a minority of patients receiving MAPK inhibitor treatment alone. Sex, serum LDH, BRAF genotype, and primary melanoma ulceration status are independent factors associated with treatment outcomes. Patients with a complete response to treatment have the best survival, but relapses still occur.
丝裂原活化蛋白激酶（MAPK）抑制剂治疗的患者反应程度和生存持续时间差异很大。基线临床病理因素能否预测治疗的临床过程在很大程度上尚不清楚。
对142例连续的、未接受过免疫治疗和MAPK抑制剂治疗的BRAF突变转移性黑色素瘤患者进行研究，这些患者在临床试验中接受了BRAF抑制剂治疗（n = 111）或达拉非尼与曲美替尼联合治疗（n = 31），分析临床病理因素与MAPK抑制剂反应及生存的相关性。
中位随访时间为15.7个月（范围0.6 - 60.5个月）。2年、3年和4年总生存率分别为43%、24%和24%。多因素分析表明，与无进展生存期（PFS）和总生存期延长相关的唯一临床病理因素是女性和治疗前血清乳酸脱氢酶（LDH）水平正常。BRAF V600E基因型和无原发性黑色素瘤溃疡也与较长的PFS独立相关，但与总生存期无关。LDH水平正常的患者中位总生存期为23.5个月，LDH水平升高的患者为7.3个月（风险比，0.31；P < 0.001）。完全缓解者生存情况最佳，但7例患者中有2例仍发生疾病进展。
少数仅接受MAPK抑制剂治疗的患者可实现长期生存。性别、血清LDH、BRAF基因型和原发性黑色素瘤溃疡状态是与治疗结果相关的独立因素。治疗完全缓解的患者生存情况最佳，但仍会出现复发。
