KRAS mutation and primary tumor location do not affect efficacy of bevacizumab-containing chemotherapy in stagae IV colorectal cancer patients

Abstract

This study aims to investigate the efficacy of bevacizumab-combined chemotherapy (BCC) in Chinese stage IV colorectal cancer (CRC), and analyze the relationship between clinicopathological features with survival. Patients with stage IV CRC treated with BCC were analyzed retrospectively. 217 metastatic CRC (mCRC) patients were collected, out of which79 were right-sided CRCs and 138 were left-sided ones. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2, single agent chemotherapy, poor/mucous/signet ring cell component, second-and further-line of bevacizumab administration, multiple metastasis sites had comparatively worse survival. Among 141 patients with known KRAS status, 55 patients harbored KRAS mutation and 86 had wild type KRAS. The ORR and DCR were 41.9% and 78.9%, respectively, in patients with wild type KRAS, while ORR and DCR was 38.7% and 77.9%, respectively, in patients with KRAS mutation. The median PFS of patients with wild type and mutant KRAS were 8.38, and9.59 months, respectively; whereas the OS was 23.00 and 21.26 months, respectively for mCRC patients with wild-type and mutant KRAS. Cumulatively, our study indicated that BCC was effective and beneficial for Chinese stage IV CRC patients. KRAS mutation status and tumor location were not a prognostic factor for survival.

Figure 1

Progression-free survival (PFS) (A) and overall survival (OS) (B) of 217 stage IV CRC treated with bevacizumab-containing chemotherapy. For details of chemotherapeutic regimen please refer to Table 1. With the median follow-up duration of 27.30 months (range, 11.99–62.52 months), the median PFS and OS were 10.05 and 20.67 months, respectively.

Figure 2

OS (A,C) and PFS (B,D) of stage IV CRC patients with different ECOG (A,B) and under different chemotherapeutic treatment regimens (C,D). Stage IV CRC patients with ECOG = 2 had significantly worse OS and PFS than patients with ECOG 0–1 (P < 0.05) (A,B). The differences of PFS and OS between oxaliplatin-based combined chemotherapies and irinotecan-based ones were not significant (P > 0.05) (C,D).

Figure 3

Effect of bevacizumab on OS and progression-free survival of stage IV CRC patients with different differentiation states (A,B), number of metastatic sites (metastatic sites ≥3 VS 1–2; (C,D)), and based on line of therapy (first line VS ≥ 2 line; (E,F)).

Figure 4

Tumor location and KRAS mutation status had no significant effect on PFS and OS of stage IV CRC receiving bevacizumab chemotherapy. OS (A,C) and PFS (B,D) of stage IV CRC patients with right- or left-sided disease (A,B) and wild type or mutant of KRAS (C,D) (P > 0.05 in each case).