Department of Medical Oncology and Hematology, Mayo Clinic, Scottsdale, AZ.
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
J Clin Oncol. 2023 Sep 1;41(25):4097-4106. doi: 10.1200/JCO.23.00434. Epub 2023 Apr 26.
Adagrasib, a KRAS inhibitor, has demonstrated clinical activity in patients with -mutated non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). mutations occur rarely in other solid tumor types. We report evaluation of the clinical activity and safety of adagrasib in patients with other solid tumors harboring a mutation.
In this phase II cohort of the KRYSTAL-1 study (ClinicalTrials.gov identifier: NCT03785249; phase Ib cohort), we evaluated adagrasib (600 mg orally twice daily) in patients with -mutated advanced solid tumors (excluding NSCLC and CRC). The primary end point was objective response rate. Secondary end points included duration of response, progression-free survival (PFS), overall survival, and safety.
As of October 1, 2022, 64 patients with -mutated solid tumors were enrolled and 63 patients treated (median follow-up, 16.8 months). The median number of prior lines of systemic therapy was 2. Among 57 patients with measurable disease at baseline, objective responses were observed in 20 (35.1%) patients (all partial responses), including 7/21 (33.3%) responses in pancreatic and 5/12 (41.7%) in biliary tract cancers. The median duration of response was 5.3 months (95% CI, 2.8 to 7.3) and median PFS was 7.4 months (95% CI, 5.3 to 8.6). Treatment-related adverse events (TRAEs) of any grade were observed in 96.8% of patients and grade 3-4 in 27.0%; there were no grade 5 TRAEs. TRAEs did not lead to treatment discontinuation in any patients.
Adagrasib demonstrates encouraging clinical activity and is well tolerated in this rare cohort of pretreated patients with -mutated solid tumors.
KRAS 抑制剂阿达格拉西布在携带 - 突变的非小细胞肺癌（NSCLC）和结直肠癌（CRC）患者中显示出临床活性。 - 突变在其他实体肿瘤类型中很少发生。我们报告了评估阿达格拉西布在携带 - 突变的其他实体肿瘤患者中的临床活性和安全性。
在 KRYSTAL-1 研究的这一 II 期队列研究（ClinicalTrials.gov 标识符：NCT03785249；Ib 期队列）中，我们评估了阿达格拉西布（每天口服 600mg，每日两次）在 - 突变的晚期实体瘤患者（不包括 NSCLC 和 CRC）中的作用。主要终点是客观缓解率。次要终点包括缓解持续时间、无进展生存期（PFS）、总生存期和安全性。
截至 2022 年 10 月 1 日，共有 64 名 - 突变的实体瘤患者入组，63 名患者接受了治疗（中位随访时间为 16.8 个月）。基线时可测量疾病的 57 名患者中，20 名（35.1%）患者观察到客观缓解（均为部分缓解），包括胰腺癌 7/21（33.3%）和胆管癌 5/12（41.7%）。缓解持续时间的中位数为 5.3 个月（95%CI，2.8 至 7.3），无进展生存期的中位数为 7.4 个月（95%CI，5.3 至 8.6）。任何级别的治疗相关不良事件（TRAEs）在 96.8%的患者中观察到，3-4 级在 27.0%的患者中观察到；没有 5 级 TRAEs。TRAEs 没有导致任何患者停止治疗。
阿达格拉西布在这一罕见的经治 - 突变的实体瘤患者队列中显示出令人鼓舞的临床活性，并且耐受性良好。
