Bevacizumab in Combination with Capecitabine plus Irinotecan as First-Line Therapy in Metastatic Colorectal Cancer: A Pooled Analysis of 2 Phase II Trials

Abstract

Background: Although phase III studies have investigated the effect of adding bevacizumab to the 3-weekly capecitabine plus irinotecan (XELIRI) combination in the first-line treatment of metastatic colorectal cancer (mCRC), no phase III studies investigating the effects of adding bevacizumab to biweekly XELIRI have been published. Patients and Methods: A retrospective pooled analysis of 2 single-arm phase II studies was performed. Previously untreated patients with mCRC received irinotecan 175 mg/m² on day 1 followed by capecitabine 1,000 mg/m² twice daily on days 2-8 every 2 weeks with or without bevacizumab 5 mg/kg on day 1. Results: In total, 53 patients received XELIRI, and 46 patients received XELIRI plus bevacizumab. There was a statistically significant increase in partial response rate with XELIRI plus bevacizumab (63 vs. 26% for XELIRI; p = 0.0002) and overall response rate (67 vs. 32%; p = 0.0005). Median time to disease progression was significantly longer with XELIRI plus bevacizumab (12.3 vs. 9.0 months for XELIRI; p = 0.012); median overall survival did not differ significantly between treatments (23.7 vs. 19.3 months; p = 0.4997). The proportion of patients experiencing at least 1 grade 3/4 adverse event was similar with both treatments (XELIRI, 47%; XELIRI plus bevacizumab, 44%). Conclusion: This retrospective pooled analysis suggests that XELIRI plus bevacizumab has an acceptable tolerability profile and improves efficacy outcomes compared with XELIRI in the first-line treatment of mCRC.

A phase I/II study of biweekly capecitabine and irinotecan plus bevacizumab as second-line chemotherapy in patients with metastatic colorectal cancer

“…Several studies have evaluated biweekly XELIRI regimens. 26 – 28 A phase II trial of a biweekly XELIRI regimen (capecitabine 2,000 mg/m 2 on days 2–8 plus irinotecan 175 mg/m 2 on day 1, every 2 weeks) obtained an objective response rate of 32%, a median time to progression of 9 months, and a median OS of 19.2 months. 27 The same regimen plus BV was evaluated in another phase II trial, which obtained a response rate of 67%, a median PFS of 12.3 months (95% CI, 6.5–18.1 months), and an OS of 23.7 months (95% CI, 16.7–30.6 months).…”

“…The planned dose intensity of irinotecan in this study (90 mg/m 2 /week) was equal to or higher than that used in previously reported biweekly XELIRI (87.5 mg/m 2 /week) or triweekly XELIRI (66.7 mg/m 2 /week) regimens, although these studies treated patients in a first-line setting. 23 , 26 As for capecitabine, the planned dose intensity was similar to that used in these previous studies. As for safety, the incidences of severe diarrhea, neutropenia, and hand–foot syndrome were acceptable despite the higher dose of irinotecan.…”

Oral drugs in the treatment of metastatic colorectal cancer

“…52 CAPIRI plus bevacizumab had an acceptable tolerability profile. [51][52][53] First-line capecitabine plus cetuximab was evaluated in elderly patients (70 years or older) with advanced CRC in a phase II trial. In patients with wild-type KRAS, capecitabine plus cetuximab combination was associated with a response rate of 48.3% and a median PFS of 8.4 months.…”

“…51–53 The addition of bevacizumab improved PFS, but not OS. 52 CAPIRI plus bevacizumab had an acceptable tolerability profile. 51–53…”

“…Several studies have examined the efficacy of capecitabine plus irinotecan (CAPIRI) plus bevacizumab as first-line treatment of patients with mCRC. 51–53 The addition of bevacizumab improved PFS, but not OS. 52 CAPIRI plus bevacizumab had an acceptable tolerability profile.…”