Doi Toshihiko, Yamaguchi Kensei, Komatsu Yoshito, Muro Kei, Nishina Tomohiro, Nakajima Takako Eguchi, Tang Rui, Yang Hui, Zhang Yilong, Jung A Scott, Ang Agnes, Yasui Hirofumi
National Cancer Center Hospital East, Kashiwa, Chiba.
Saitama Cancer Center, Kita Adachi-gun, Saitama.
Jpn J Clin Oncol. 2017 Nov 1;47(11):1002-1009. doi: 10.1093/jjco/hyx114.
To evaluate the safety (including adverse events and dose-limiting toxicities [DLTs]), tolerability, pharmacokinetics and antitumor activity of the investigational MET inhibitor rilotumumab alone in patients with advanced solid tumors (Part 1) or in combination with cisplatin plus capecitabine (CX) in patients with MET-positive advanced gastric or gastroesophageal junction cancer (Part 2).
Adult patients received 10 or 20 mg/kg intravenous (IV) rilotumumab every 2 weeks (Part 1) or 15 mg/kg IV rilotumumab every 3 weeks plus 80 mg/m2 cisplatin on Day 1 and 1000 mg/m2 capecitabine twice daily on Days 1-14 of every 21-day cycle (Part 2).
Nine patients enrolled in Part 1; 12 patients enrolled in Part 2. One DLT occurred (Grade 3 decreased appetite and stomatitis [Part 2]). Adverse events related to any treatment occurred in 17 patients (81%) and were Grade ≥3 in nine patients (43%). Rilotumumab pharmacokinetics appeared linear, and exposure was unaffected by CX. No patient who received rilotumumab monotherapy in Part 1 had a response. In Part 2, five of eight patients (63%) with measureable disease at baseline had a partial response and two patients (25%) had stable disease; median (95% CI) progression-free survival was 7.0 (2.4-15.4) months; overall survival was 18.2 (5.6-20.4) months.
In combination with CX, rilotumumab appeared tolerable and showed antitumor activity in Japanese patients with MET-positive gastric/gastroesophageal junction cancer. However, owing to the results of recent Phase 3 trials of MET inhibitors (including rilotumumab), further development of rilotumumab in this setting is not being pursued. ClinicalTrials.gov Identifier: NCT01791374.
评估研究性MET抑制剂rilotumumab单药用于晚期实体瘤患者（第1部分）或与顺铂加卡培他滨（CX）联合用于MET阳性晚期胃癌或胃食管交界癌患者（第2部分）的安全性（包括不良事件和剂量限制性毒性[DLTs]）、耐受性、药代动力学及抗肿瘤活性。
成年患者每2周接受10或20mg/kg静脉注射（IV）rilotumumab（第1部分），或每3周接受15mg/kg IV rilotumumab，同时在每21天周期的第1天给予80mg/m²顺铂，在第1 - 14天每天2次给予1000mg/m²卡培他滨（第2部分）。
第1部分入组9例患者；第2部分入组12例患者。发生1例DLT（3级食欲减退和口腔炎[第2部分]）。17例患者（81%）发生与任何治疗相关的不良事件，其中9例患者（43%）为≥3级。Rilotumumab的药代动力学呈线性，且暴露不受CX影响。第1部分接受rilotumumab单药治疗的患者均无反应。在第2部分，8例基线时疾病可测量的患者中有5例（63%）部分缓解，2例患者（25%）病情稳定；无进展生存期的中位数（95%CI）为7.0（2.4 - 15.4）个月；总生存期为18.2（5.6 - 20.4）个月。
与CX联合使用时，rilotumumab在日本MET阳性胃癌/胃食管交界癌患者中似乎耐受性良好且显示出抗肿瘤活性。然而，由于近期MET抑制剂（包括rilotumumab）的3期试验结果，不再在此情况下进一步研发rilotumumab。ClinicalTrials.gov标识符：NCT01791374。
