演題

転移性結腸直腸癌(mCRC)の日本人患者を対象としたアフリベルセプト+FOLFIRIの第II相試験

[演者] 宇良 敬:1
[著者] 傳田 忠道:2, 佐藤 太郎:3, 濱口 哲弥:4, 杉本 直俊:5, 佐々木 亨:6, 須永 義則:6, 吉野 孝之:7
1:愛知県がんセンター中央病院 薬物療法部, 2:千葉県がんセンター 消化器内科, 3:大阪大学大学院医学系研究科 先進癌薬物療法開発学寄附講座, 4:国立がん研究センター中央病院 消化管内科, 5:大阪府立成人病センター 臨床腫瘍科, 6:サノフィ株式会社, 7:国立がん研究センター東病院 消化管内科

Background
Aflibercept (AF) blocks VEGF-A/B and placental growth factor, and AF+FOLFIRI is a second line therapy for mCRC. This open-label, multicenter phase 2 study aimed to assess the efficacy, safety and pharmacokinetics (PK) of AF + FOLFIRI post-oxaliplatin in mCRC patients (pts) in Japan and to identify prognostic biomarkers.

Methods
Pts received AF (4 mg/kg) + FOLFIRI (180 mg/m2 irinotecan) every 2 weeks until disease progression, unacceptable toxicity or study withdrawal. Primary endpoint: overall response rate (ORR). Secondary endpoints: PFS, OS and safety. Tumors were assessed by independent reviewers every 6±1 weeks until progression. Blood was drawn pre- and during treatment Cycle 1, and PK data were calculated. Plasma levels of 78 potential protein biomarkers with roles in tumor progression were measured at baseline and pre-dose 3 in all pts by enzyme-linked immunosorbent assays. Relationships between these levels and efficacy were assessed.

Results
62 pts were enrolled. The ORR was 8.3% (95% CI: 1.3-15.3%). Median PFS was 5.4 months (95% CI: 4.1-6.7); median OS was 15.6 months (range 11.2-19.8). 41 pts (66.1%) died due to disease progression; 0 died due to adverse event. Grade 3-4 toxicity were neutropenia, hypertension, diarrhea and decreased appetite. Free AF cleared at 0.7±0.2 L/day. Baseline levels of 8 potential biomarkers correlated with OS in a univariate Cox regression (multiplicity adjusted P<.05): tissue inhibitor of metalloproteinases 1, interleukin 8, extracellular newly identified receptor for advanced glycation end-products binding protein (BP), pulmonary surfactant-associated protein D, tenascin-C, insulin-like growth factor BP 1, kallikrein 5 and tumor necrosis factor receptor 2. No other correlations between biomarkers and efficacy were found.

Conclusions
The ORR was 8.3%. No new significant finding in Safety, PK data and drug interactions. 8 biomarkers studied could be associated with OS in Japanese population. Clinical trial NCT01882868.
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