Taylor Matthew H, Alva Ajjai S, Larson Timothy, Szpakowski Sebastian, Purkaystha Das, Amin Alpesh, Karpiak Linda, Piha-Paul Sarina A
Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI, USA.
Oncotarget. 2020 Apr 7;11(14):1235-1243. doi: 10.18632/oncotarget.27530.
Receptor tyrosine kinases (RTKs) play key roles in tumorigenesis. The multi-RTK inhibitor dovitinib has demonstrated promising antitumor activity in multiple cancers.
In this phase 2, open-label, single-arm study, patients with advanced malignancies with RTK-pathway genetic aberrations whose disease progressed on/following standard treatment received dovitinib (500 mg/day; 5-days-on/2-days-off). The primary endpoint was clinical benefit rate (CBR; complete response, partial response [PR], or stable disease [SD] for ≥ 16 weeks).
Of 80 patients enrolled, common tumors included gastrointestinal stromal tumors (GIST; 20.0%), colorectal cancer (CRC; 18.8%), and ovarian cancer (10.0%). Patients were heavily pretreated (median prior lines = 4; 67.5% had ≥ 3 prior lines). Genetic aberrations included (28.8%), (15.0%), and (15.0%). The CBR was 13.8%; one PR (GIST) and 10 SD (adenoid cystic [ = 3]; ovarian [ = 3]; GIST [ = 2]; CRC [ = 1]; gastroesophageal junction [ = 1]). The most common treatment-related adverse events were fatigue, diarrhea, nausea, and vomiting.
In this heterogeneous patient population, the safety profile was acceptable for dovitinib therapy. A subset of patients with RTK pathway-activated tumors experienced clinical benefit. However, the primary endpoint was not met, suggesting further refinement of predictive biomarkers is required.
受体酪氨酸激酶（RTK）在肿瘤发生中起关键作用。多靶点RTK抑制剂多韦替尼在多种癌症中已显示出有前景的抗肿瘤活性。
在这项2期、开放标签、单臂研究中，患有RTK通路基因异常且疾病在标准治疗期间或之后进展的晚期恶性肿瘤患者接受多韦替尼治疗（500毫克/天；服用5天，停药2天）。主要终点是临床获益率（CBR；完全缓解、部分缓解[PR]或疾病稳定[SD]≥16周）。
入组的80例患者中，常见肿瘤包括胃肠道间质瘤（GIST；20.0%）、结直肠癌（CRC；18.8%）和卵巢癌（10.0%）。患者接受过大量前期治疗（中位前期治疗线数 = 4；67.5%有≥3条前期治疗线）。基因异常包括（28.8%）、（15.0%）和（15.0%）。CBR为13.8%；1例PR（GIST）和10例SD（腺样囊性癌[ = 3]；卵巢癌[ = 3]；GIST[ = 2]；CRC[ = 1]；胃食管交界癌[ = 1]）。最常见的治疗相关不良事件为疲劳、腹泻、恶心和呕吐。
在这个异质性患者群体中，多韦替尼治疗的安全性可接受。一部分RTK通路激活的肿瘤患者有临床获益。然而，未达到主要终点，提示需要进一步优化预测生物标志物。
