Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Dana-Farber Cancer Institute, ECOG-ACRIN Biostatistics Center, Boston, MA.
JCO Precis Oncol. 2022 Feb;6:e2100424. doi: 10.1200/PO.21.00424.
mutations frequently contribute to oncogenesis in solid tumors. Taselisib, a potent and selective inhibitor of phosphoinositide 3-kinase, has demonstrated clinical activity in -mutant breast cancer. Whether mutations predict sensitivity to taselisib in other cancer types is unknown. National Cancer Institute-Molecular Analysis for Therapy Choice Arm EAY131-I is a single-arm, phase II study of the safety and efficacy of taselisib in patients with advanced cancers.
Eligible patients had tumors with an activating mutation. Patients with breast or squamous cell lung carcinoma, or whose cancer had or mutations, were excluded. Patients received taselisib 4 mg, orally once daily continuously, until disease progression or unacceptable toxicity. The primary end point was objective response rate. Secondary end points included progression-free survival (PFS), 6-month PFS, overall survival (OS), and identification of predictive biomarkers.
Seventy patients were enrolled, and 61 were eligible and initiated protocol therapy. Types of mutations included helical 41 of 61 (67%), kinase 11 of 61 (18%), and other 9 of 61 (15%). With a median follow-up of 35.7 months, there were no complete or partial responses. Six-month PFS was 19.9% (90% CI, 12.0 to 29.3) and median PFS was 3.1 months (90% CI, 1.8 to 3.7). Six-month OS was 60.7% (90% CI, 49.6 to 70.0) and median OS was 7.2 months (90% CI, 5.9 to 10.0). Individual comutations were too heterogeneous to correlate with clinical outcome. Fatigue, diarrhea, nausea, and hyperglycemia were the most common toxicities, and most were grade 1 and 2.
In this study, taselisib monotherapy had very limited activity in a heterogeneous cohort of heavily pretreated cancer patients with -mutated tumors; the presence of a mutation alone does not appear to be a sufficient predictor of taselisib activity.
突变经常导致实体肿瘤的发生。Taselisib 是一种有效的、选择性的磷酸肌醇 3-激酶抑制剂，在 - 突变型乳腺癌中显示出临床活性。是否存在 突变可以预测其他癌症类型对 taselisib 的敏感性尚不清楚。美国国立癌症研究所 - 分子分析治疗选择臂 EAY131-I 是一项 taselisib 在晚期癌症患者中的安全性和疗效的单臂、二期研究。
符合条件的患者有激活 突变的肿瘤。患有乳腺癌或鳞状细胞肺癌的患者，或其癌症有 或 突变的患者被排除在外。患者每天口服 taselisib 4 毫克，连续使用，直到疾病进展或出现不可接受的毒性。主要终点是客观缓解率。次要终点包括无进展生存期（PFS）、6 个月 PFS、总生存期（OS）和预测生物标志物的确定。
70 名患者入组，61 名符合条件并开始接受方案治疗。61 名患者中，61 名（67%）为螺旋 41 突变，61 名（18%）为激酶 11 突变，61 名（15%）为其他 9 突变。中位随访 35.7 个月，无完全或部分缓解。6 个月 PFS 为 19.9%（90%CI，12.0 至 29.3），中位 PFS 为 3.1 个月（90%CI，1.8 至 3.7）。6 个月 OS 为 60.7%（90%CI，49.6 至 70.0），中位 OS 为 7.2 个月（90%CI，5.9 至 10.0）。个别 comutations 过于混杂，无法与临床结果相关。疲劳、腹泻、恶心和高血糖是最常见的毒性反应，大多数为 1 级和 2 级。
在这项研究中，taselisib 单药治疗在一组异质性的、预处理过的、携带有 突变的肿瘤的癌症患者中活性非常有限；单独存在 突变似乎不能充分预测 taselisib 的活性。
