Gien Lilian T, Song Zihe, Poklepovic Andrew, Collisson Eric A, Zwiebel James A, Gray Robert J, Wang Victoria, McShane Lisa M, Rubinstein Larry V, Patton David R, Williams P Mickey, Hamilton Stanley R, Tricoli James V, Conley Barbara A, Arteaga Carlos L, Harris Lyndsay N, O'Dwyer Peter J, Chen Alice P, Flaherty Keith T
Odette Cancer Centre-Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Dana Farber Cancer Institute, ECOG-ACRIN Biostatistics Center, Boston, MA.
JCO Precis Oncol. 2024 Dec;8:e2400514. doi: 10.1200/PO-24-00514. Epub 2024 Dec 12.
The NCI-MATCH study is a tumor-agnostic platform trial enrolling patients to targeted therapies on the basis of genomic alterations. Subprotocol V investigated sunitinib in patients with tumors harboring - mutations.
EAY131-V, is an open-label, single-arm, phase II study. Eligible patients had malignancies containing somatic mutation on exons 9, 11, 13, or 14. Exclusions were mutations on exons 17 and 18, gastrointestinal stromal tumors, renal cell carcinoma, and pancreatic neuroendocrine tumors. Patients received sunitinib 50 mg orally once daily for 4 weeks with 2-week rest per cycle, until disease progression or unacceptable toxicity. Primary end point was objective response rate (ORR); secondary end points were progression-free survival (PFS) at 6 months, PFS, overall survival, and toxicities.
Between November 1, 2016, and May 21, 2020, 10 patients were enrolled and nine were eligible and started treatment. The median age was 62 years (range, 30-76), 77.8% received two previous lines of systemic therapy, and 22.2% received >3 lines. The most common histology was melanoma (44%) and then squamous cell carcinoma of the lung or thymus (33%). There were two partial responses with an ORR of 22.2% (90% CI, 4.1 to 55) and stable disease in 44%. All patients demonstrated tumor shrinkage of target lesions. The estimated 6-month PFS was 33.3% (90% CI, 15.4 to 72.4). Grade 3-4 toxicities occurred in five patients (55.6%). This arm was closed in 2022 on the basis of low accrual. Prevalence of eligible mutations after screening 5,540 patients was 0.45%.
Sunitinib for mutations did not meet the primary end point, but in this small sample size, a potential signal cannot be ruled out. Rate of eligible mutations was low, affecting accrual to this arm.
NCI-MATCH研究是一项不区分肿瘤类型的平台试验，根据基因组改变为患者提供靶向治疗。子方案V研究了舒尼替尼在携带-突变肿瘤患者中的应用。
EAY131-V是一项开放标签、单臂、II期研究。符合条件的患者患有外显子9、11、13或14上存在体细胞突变的恶性肿瘤。排除标准为外显子17和18上的突变、胃肠道间质瘤、肾细胞癌和胰腺神经内分泌肿瘤。患者接受舒尼替尼50mg口服，每日一次，共4周，每周期休息2周，直至疾病进展或出现不可接受的毒性。主要终点是客观缓解率（ORR）；次要终点是6个月时的无进展生存期（PFS）、PFS、总生存期和毒性。
2016年11月1日至2020年5月21日，共入组10例患者，9例符合条件并开始治疗。中位年龄为62岁（范围30-76岁），77.8%的患者接受过两线全身治疗，22.2%的患者接受过三线以上治疗。最常见的组织学类型是黑色素瘤（44%），其次是肺或胸腺鳞状细胞癌（33%）。有2例部分缓解，ORR为22.2%（90%CI，4.1至55），44%的患者病情稳定。所有患者的靶病灶均出现肿瘤缩小。估计6个月的PFS为33.3%（90%CI，15.4至72.4）。5例患者（55.6%）出现3-4级毒性。由于入组率低，该组于2022年关闭。在筛查5540例患者后，符合条件的-突变患病率为0.45%。
舒尼替尼治疗-突变未达到主要终点，但在这个小样本量中，不能排除潜在信号。符合条件的-突变率较低，影响了该组的入组。
