ASCO 2019原文：
https://meetinglibrary.asco.org/record/169362/abstract
Efficacy and safety of dabrafenib (D) and trametinib (T) in patients(pts) with BRAF V600E–mutated biliary tract cancer(BTC): A cohort of the ROAR basket trial.
Presented Friday,January 18, 2019
Background:BTCs are rare, aggressive malignancies with poor prognoses. Treatment options and outcomes after first-line therapy are not well defined. Median progression-free survival (PFS) in second-line BTC is < 5 mo. Combined BRAF + MEK inhibition is efficacious in BRAF V600–mutated anaplastic thyroid cancer, melanoma, and lung cancer, but less so in BRAF V600E-mutated colorectal cancer. Activating BRAF V600E mutations have been reported in 0% to 20% of BTCs; thus, D (BRAF inhibitor) + T (MEK inhibitor) was evaluated as a treatment for pts with BRAF V600E–mutated BTC in the ROAR basket trial.
胆管癌是一种罕见的恶性肿瘤，预后差，一线治疗后的治疗选择和结果尚不明确，胆管癌二线治疗的中位无进展生存期(PFS)小于5个月。联合BRAF+MEK抑制对BRAF V600E突变的甲状腺未分化癌、黑色素瘤和肺癌有效，但对BRAF V600E突变的结直肠癌效果不明显。据报道，0-20%的胆管癌患者中有BRAF V600E突变。因此，在ROAR试验中，将评估D达拉非尼（BRAF抑制剂）联合曲美替尼T(MEK抑制剂)对BRAF V600E突变的胆管癌患者治疗的有效性和安全性。
Methods:In this phase II, open-label trial, pts with BRAF V600E mutations in 9 rare tumor types, including BTC, received D (150 mg BID) + T (2 mg QD) until unacceptable toxicity, disease progression, or death. Eligible pts had advanced or metastatic cancer and had been treated with ≥ 1 prior systemic therapy. The primary endpoint was investigator-assessed overall response rate (ORR). Secondary endpoints included duration of response (DOR), PFS, overall survival (OS), biomarker correlates, and safety.
在第Ⅱ期开放试验中，9种罕见肿瘤类型（包括胆管癌）的BRAF V600E突变患者将接受D(150mg,bid)+T(2mg,qd)治疗，直至出现不可耐受的毒性、疾病进展或死亡。符合条件的患者有晚期或转移性肿瘤，并接受过1次以上的全身治疗。主要终点是评估客观缓解率(ORR)，次要终点包括缓解持续时间(DOR)、无进展生存期(PFS)、总生存期(OS)、生物标志物相关性和安全性。Results:Thirty-three pts with BTC had enrolled at data cutoff (January 3, 2018). BRAF V600E mutations were centrally confirmed in 30 of 33 pts with BTC (91%). Median age was 58 y, and 78% had received ≥ 2 prior lines of systemic therapy. 32 of 33 pts with BTC were evaluable. Investigator-assessed ORR was 41% (13/32; 95% CI, 24%-59%), with 6 of 13 responses ongoing at data cutoff, 7 of 13 pts (54%) had a DOR ≥ 6 mo. Median PFS was 7.2 mo (95% CI, 4.6-10.1 mo), and median OS was 11.3 mo (95% CI, 7.3-17.6 mo). Grade 3/4 adverse events in ≥ 3 pts were increased γ-glutamyltransferase (n = 3 [9%]) and decreased white blood cell count (n = 3 pts [9%]). Biomarker analyses demonstrate a heterogeneous genetic landscape, and suggest a higher baseline expression of MAPK pathway genes in the pts who did not respond to D + T.
共登记了33名胆管癌患者（2018年1月3日），有30名（91%）患者检测出BRAF V600E突变，平均年龄58岁，78%的患者先接受2次及以上系统治疗。最终32名患者被评估，研究评估的客观缓解率ORR为41%(13/32; 95% CI, 24%-59%)，同时在数据截止时，13名患者中有6名患者仍在接受治疗，7名(54%)患者缓解持续时间≥6个月。中位无进展生存期PFS为7.2个月(95% CI，4.6~10.1月)，中位总生存期OS为11.3个月(95% CI 7.3~17.6个月)。在≥3名患者中发生了3/4级不良反应事件，包括γ-谷氨酰转移酶升高(n = 3 [9%])和白细胞计数下降(n = 3 pts [9%]))。生物标志物分析显示了一个异质性的遗传全景，并提示在对达拉非尼联曲美替尼无反应的患者中MAPK通路基因的基线表达更高。Conclusions:D + T demonstrated promising efficacy in pts with BTC, with a favorable safety profile. These pts should be considered for BRAF mutation analysis, and D + T should be considered for pts with BRAF V600E-mutated BTC.
D + T在胆管癌患者中显示出良好的疗效，具有良好的安全性。胆管癌患者应考虑进行BRAF基因突变分析。BRAF V600E突变的胆管癌患者应考虑达拉非尼联合曲美替尼的治疗方案。
Clinical trial information: NCT02034110
更多临床信息请参考：
https://clinicaltrials.gov/ct2/show/NCT02034110
BRAF V600E 胆管癌案例
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