Northwestern University, Chicago, IL.
Dana Farber Cancer Institute-ECOG-ACRIN Biostatistics Center, Boston, MA.
J Clin Oncol. 2020 Jul 20;38(21):2407-2417. doi: 10.1200/JCO.19.02630. Epub 2020 May 28.
NCI-MATCH is a nationwide, histology-agnostic, signal-finding, molecular profile-driven trial for patients with refractory cancers, lymphomas, or myelomas. Patients with tumors harboring actionable aberration(s) in fibroblast growth factor receptor () were treated with AZD4547, an oral FGFR1-3 inhibitor.
Patients' tumors were screened by next-generation sequencing for predefined amplification, activating mutations, or fusions. Patients were treated with AZD4547, 80 mg orally twice daily until progression of disease or drug intolerance. A response rate of 16% was considered promising.
Between July 2016 and June 2017, 70 patients were assigned and 48 received protocol therapy and are eligible for analysis. Patients' tumors harbored or amplification (n = 20), or single-nucleotide variants (n = 19), or or fusions (n = 9). The most common primary tumors were breast (33.3%), urothelial (12.5%), and cervical cancer (10.4%).Grade 3 adverse events were consistent with those described in previous clinical trials. Confirmed partial responses were seen in 8% (90% CI, 3% to 18%) and were observed only in patients whose tumors harbored point mutations or fusions. Stable disease was observed in 37.5% (90% CI, 25.8% to 50.4%). The median progression-free survival (PFS) was 3.4 months, and the 6-month PFS rate was 15% (90% CI, 8% to 31%). For patients with tumors harboring fusions, the response rate was 22% (90% CI, 4.1% to 55%), and 6-month PFS rate was 56% (90% CI, 31% to 100%).
Preliminary signals of activity appeared to be limited to cancers harboring activating mutations and fusions, although AZD4547 did not meet the primary end point. Different somatic alterations may confer different levels of signaling potency and/or oncogene dependence.
NCI-MATCH 是一项针对难治性癌症、淋巴瘤或骨髓瘤患者的全国性、组织学非特异性、信号发现、分子谱驱动的试验。携带成纤维细胞生长因子受体 () 种活性变异的肿瘤患者接受了口服 FGFR1-3 抑制剂 AZD4547 治疗。
通过下一代测序对患者的肿瘤进行筛查，以确定是否存在预先定义的 扩增、激活突变或融合。患者接受 AZD4547 治疗，每日口服 80mg，每日两次，直至疾病进展或药物不耐受。16%的缓解率被认为是有希望的。
2016 年 7 月至 2017 年 6 月期间，共分配了 70 名患者，其中 48 名患者接受了方案治疗，并符合分析条件。患者的肿瘤携带 或 扩增（n=20）、 或 单核苷酸变异（n=19）或 或 融合（n=9）。最常见的原发肿瘤是乳腺癌（33.3%）、尿路上皮癌（12.5%）和宫颈癌（10.4%）。3 级不良事件与先前临床试验中描述的一致。仅在肿瘤携带 点突变或融合的患者中观察到确认的部分缓解，缓解率为 8%（90%CI，3%至 18%）。观察到稳定疾病的患者占 37.5%（90%CI，25.8%至 50.4%）。中位无进展生存期（PFS）为 3.4 个月，6 个月 PFS 率为 15%（90%CI，8%至 31%）。对于携带 融合的肿瘤患者，缓解率为 22%（90%CI，4.1%至 55%），6 个月 PFS 率为 56%（90%CI，31%至 100%）。
尽管 AZD4547 未达到主要终点，但初步的活性信号似乎仅限于携带 激活突变和融合的癌症。不同的 体细胞改变可能赋予不同水平的信号转导能力和/或致癌基因依赖性。
