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. 2019 Mar;12(3):502-512.
doi: 10.1016/j.tranon.2018.12.003. Epub 2018 Dec 27.

Oncologic Outcomes in Metastatic Colorectal Cancer with Regorafenib with FOLFIRI as a Third- or Fourth-Line Setting

Cheng-Jen Ma  1 , Ching-Wen Huang  2 , Tsung-Kun Chang  3 , Hsiang-Lin Tsai  4 , Wei-Chih Su  5 , Yung-Sung Yeh  6 , Po-Jung Chen  7 , Jaw-Yuan Wang  8
Affiliations

Oncologic Outcomes in Metastatic Colorectal Cancer with Regorafenib with FOLFIRI as a Third- or Fourth-Line Setting

Cheng-Jen Ma et al. Transl Oncol. 2019 Mar.

Abstract

Background: To evaluate the efficacy and toxicities of regorafenib plus irinotecan, dose-escalated on the basis of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping, in previously heavily treated metastatic colorectal cancer (mCRC) and the prognostic values of EGFR expression, KRAS mutations, and tumor sidedness.

Methods: Forty-one patients with mCRC with disease progression after treatment with fluoropyrimidines, oxaliplatin, irinotecan, anti-VEGF, and anti-EGFR MoAbs were subjected to UGT1A1 genotyping and received regorafenib combined with FOLFIRI with dose-escalated irinotecan.

Results: The median follow-up period was 10.0 months (1.3-23.5 months). The overall disease control rate was 58.5%, whereas the median progression-free survival (PFS) and overall survival (OS) were 6.0 months and 12.0 months, respectively. KRAS mutations were significantly associated with positive EGFR expression (P = .026). KRAS mutations significantly correlated with a shorter OS than KRAS wild-type (6.0 vs. 14.4 months, P = .014) but had no significant association with PFS. Positive EGFR expression had an inverse correlation with PFS (2.5 vs. 14.0 months, P = .039) and OS (9.6 vs. 19.7 months, P = .044). Moreover, left-sided tumors associated with superior PFS (2.0 vs. 7.0 months, P < .0001) and OS (4.0 vs. 13.0 months, P < .0001), and tumor sidedness was an independent prognostic factor by the multivariate analysis.

Conclusion: Regorafenib and FOLFIRI concomitant therapy with dose-escalated irinotecan seemed to be potentially practicable with satisfactory oncological results. KRAS mutations and EGFR expression might be predictors of poor oncological outcomes; however, left-sided mCRCs would be more beneficial for concomitant regorafenib and FOLFIRI therapy.

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Figures

Figure 1
Figure 1
The study scheme of the present study.
Figure 2
Figure 2
Kaplan-Meier survival analysis of all patients with metastatic colorectal cancer. (A) Progression-free survival and (B) overall survival.
Figure 3
Figure 3
Kaplan-Meier survival analysis of KRAS subgroups. (A) Progression-free survival and (B) overall survival.
Figure 4
Figure 4
Kaplan-Meier survival analysis of EGFR expression subgroups. (A) Progression-free survival and (B) overall survival.
Figure 5
Figure 5
Kaplan-Meier survival analysis of tumor sidedness subgroups. (A) Progression-free survival and (B) overall survival.
See this image and copyright information in PMC

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