Role of KRAS Mutations in Patients with Metastatic Colorectal Cancer Who Receive Regorafenib Plus FOLFIRI as a Salvage Therapy

Purpose. The aim of this study was to evaluate the role of KRAS status in patients with metastatic colorectal cancer (mCRC) who received regorafenib plus irinotecan dose-escalated folinic acid, fluorouracil, and irinotecan (FOLFIRI) as a salvage therapy. Methods. Between October 2013 and June 2017, 21 patients with mCRC from a single institution were retrospectively reviewed for their clinical features and the efficacy of regorafenib plus irinotecan dose-escalated FOLFIRI as a salvage therapy. Patients’ progression-free survival (PFS), overall survival (OS), and subgroup analysis results were compared among KRAS categories. Results. The median follow-up period was 10.0 months (1.3-38.6 months), and the median PFS and OS of all patients were 7.0 and 10.0 months, respectively. The disease control rate (DCR) was 61.9%, comprising 9.5% of partial response and 52.4% of stable disease. Regarding outcomes, patients with wild-type KRAS tumors exhibited a trend toward a better median PFS (7.0 vs. 5.5 months, p = 0.494) and OS (13.0 vs. 9.5 months, p = 0.249) compared with those with mutant-type KRAS tumors, although this result was not statistically significant. The subgroup analysis conducted according to KRAS status also revealed no significant correlation with the patients' sex, age, UGT1A1 status, irinotecan dosage, treatment response, DCR, and hand-foot syndrome occurrence rate. Conclusions. The combination therapy of regorafenib plus FOLFIRI may yield a promising DCR and prominent median PFS and OS. The regorafenib plus irinotecan-based regimen had favorable clinical outcomes in patients with wild-type KRAS mCRC, although the result was not statistically significant.

關鍵字

Regorafenib ； FOLFIRI ； KRAS ； Metastatic colorectal cancer

並列摘要

目的：本研究的目的在於評估KRAS基因的角色在接受regorafenib及irinotecan劑量調整過的FOLFIRI當作救援治療的轉移性大腸直腸癌病人。方法：以單一醫學中心，從2013年10月至2017年6月，總共收錄了21位病人。回顧性的記錄其臨床特徵及以regorafenib及irinotecan劑量調整過的FOLFIRI當作救援治療的療效。其無進展生存期、總生存期依據KRAS基因做出分組分析。結果：經過10.0個月(1.3-38.6個月)中位數追蹤時間，全部病人的中位數無進展生存期及總生存期分別為7.0及10.0個月。疾病控制率為61.9%，其中包含有9.5%的病人疾病程度為部分改善及52.4%為穩定疾病。在KRAS基因野生型及突變型之間，兩個族群的中位數無進展生存期(野生型7.0個月對比突變型5.5個月，p值等於0.494)及中位數總生存期(野生型13.0個月對比突變型9.5個月，p值等於0.249)。兩組病人的性別、年齡、UGT1A1基因型、irinotecan劑量、治療反應、疾病控制率及手足症候群發生率亦均無統計學上的顯著差異。結論：針對轉移性大腸直腸癌病人以regorafenib及irinotecan劑量調整過的FOLFIRI的合併治療可以得到較好的疾病控制率及較長的無進展生存期及總生存期。而KRAS基因野生型的轉移性大腸直腸癌病人在接受此合併療法後顯示出無統計學上差異但仍有較好的治療趨勢。

並列關鍵字

regorafenib ； FOLFIRI ； KRAS ；轉移性大腸直腸癌

參考文獻

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國際替代計量

Role of KRAS Mutations in Patients with Metastatic Colorectal Cancer Who Receive Regorafenib Plus FOLFIRI as a Salvage Therapy

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