Identifying treatment options for BRAFV600 wild-type metastatic melanoma: A SU2C/MRA genomics-enabled clinical trial.
Identifying treatment options for BRAFV600 wild-type metastatic melanoma: A SU2C/MRA genomics-enabled clinical trial.
复制标题
DOI：
10.1371/journal.pone.0248097
复制
发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Trent JM
中科院分区：
文献类型：
--
作者：
LoRusso PM;Sekulic A;Sosman JA;Liang WS;Carpten J;Craig DW;Solit DB;Bryce AH;Kiefer JA;Aldrich J;Nasser S;Halperin R;Byron SA;Pilat MJ;Boerner SA;Durecki D;Hendricks WPD;Enriquez D;Izatt T;Keats J;Legendre C;Markovic SN;Weise A;Naveed F;Schmidt J;Basu GD;Sekar S;Adkins J;Tassone E;Sivaprakasam K;Zismann V;Calvert VS;Petricoin EF;Fecher LA;Lao C;Eder JP;Vogelzang NJ;Perlmutter J;Gorman M;Manica B;Fox L;Schork N;Zelterman D;DeVeaux M;Joseph RW;Cowey CL;Trent JM
尽管 BRAF 和 MEK 抑制剂组合对 40-50% 携带 BRAFV600 突变的皮肤转移性黑色素瘤非常有效，但靶向药物对 BRAFV600 野生型 (wt) 转移性黑色素瘤无效。 SU2C 黑色素瘤基因组医学试验采用西蒙两阶段优化设计来评估全面的基因组分析是否可以改善在标准护理治疗（可能包括免疫治疗）中取得进展的 BRAFV600wt 转移性黑色素瘤患者的分子疗法选择。在可评估疗效的患者中，20 名患者选择了 binimetinib，随机分配到基因组学组，9 名患者接受替代治疗组治疗。接受针对性建议治疗的 27 名患者的缓解率包括 1 名 (4%) 部分缓解、18 名 (67%) 疾病稳定、8 名 (30%) 疾病进展。试验后基因组和蛋白质通路激活图谱确定了未来研究可能考虑的其他药物类别。我们的结果强调了转移性黑色素瘤的复杂性和异质性，以及该试验中缺乏反应可能与单一疗法药物选择和缺乏可用的单一和组合分子驱动疗法来治疗 BRAFV600wt 转移性黑色素瘤有关。
Although combination BRAF and MEK inhibitors are highly effective for the 40–50% of cutaneous metastatic melanomas harboring BRAFV600 mutations, targeted agents have been ineffective for BRAFV600wild-type (wt) metastatic melanomas. The SU2C Genomics-Enabled Medicine for Melanoma Trial utilized a Simon two-stage optimal design to assess whether comprehensive genomic profiling improves selection of molecular-based therapies for BRAFV600wt metastatic melanoma patients who had progressed on standard-of-care therapy, which may include immunotherapy. Of the response-evaluable patients, binimetinib was selected for 20 patients randomized to the genomics-enabled arm, and nine were treated on the alternate treatment arm. Response rates for 27 patients treated with targeted recommendations included one (4%) partial response, 18 (67%) with stable disease, and eight (30%) with progressive disease. Post-trial genomic and protein pathway activation mapping identified additional drug classes that may be considered for future studies. Our results highlight the complexity and heterogeneity of metastatic melanomas, as well as how the lack of response in this trial may be associated with limitations including monotherapy drug selection and the dearth of available single and combination molecularly-driven therapies to treat BRAFV600wt metastatic melanomas.
登录
查看更多内容
影响因子：
3.7
作者：
Ding L;Kim M;Kanchi KL;Dees ND;Lu C;Griffith M;Fenstermacher D;Sung H;Miller CA;Goetz B;Wendl MC;Griffith O;Cornelius LA;Linette GP;McMichael JF;Sondak VK;Fields RC;Ley TJ;Mulé JJ;Wilson RK;Weber JS
通讯作者：
Weber JS
影响因子：
30.8
作者：
Krauthammer M;Kong Y;Bacchiocchi A;Evans P;Pornputtapong N;Wu C;McCusker JP;Ma S;Cheng E;Straub R;Serin M;Bosenberg M;Ariyan S;Narayan D;Sznol M;Kluger HM;Mane S;Schlessinger J;Lifton RP;Halaban R
通讯作者：
Halaban R
影响因子：
50.5
作者：
Hersh, E. M.;Del Vecchio, M.;Hauschild, A.
通讯作者：
Hauschild, A.
影响因子：
8.8
作者：
Bendell, Johanna C.;Javle, Milind;Patnaik, Amita
通讯作者：
Patnaik, Amita
影响因子：
45.3
作者：
Chapman, PB;Einhorn, LH;Kirkwood, JM
通讯作者：
Kirkwood, JM