Chinese Clinical Oncology

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Efficacy and safety of bevacizumab in combination with fluoropyrimidine-based chemotherapy for the treatment of advanced metastatic colorectal cancer: a prospective, non-intervention and post-marketing multicenter clinical study(REACT)

EACT Clinical Research Group:QIN Shukui,DENG Yanhong,BI Feng, LIU Tianshu, LIU Yunpeng, ZHANG Suzhan, XU Jianming, SHU Yongqian, XU Nong, WU Changping, WANG Xin, ZHONG Haijun,FENG Jifeng,HE Yulong,YANG Jianwei.   

  • Received:2016-09-16 Revised:2016-09-30 Online:2016-10-30 Published:2016-10-30
  • Contact: QIN Shukui

Abstract: Background & ObjectiveBevacizumab(BV)combined with fluorouracil drugsbased chemotherapy for metastatic colorectal cancer (mCRC) acting as a standard therapy has been recognized and practiced in European and America. Post-marketing surveillance of patients who received BV was required because of very limited clinical data, especially safety profile in China pts. In order to understand real world practical use of BV and guide clinical practice in China,we have studied safety and efficacy of BV combined with fluorouracil based chemotherapy (CT) in 1st- or 2nd-line treatment for pts with mCRC in REACT trial (REal world study of Avastin in ColorecTal cancer;Clinical Trail No. NCT01319877). Methods That study was a prospective, non-interventional and post-marketing multicenter study conducted in 24 Chinese cancer centers. Patients were treated with BV plus fluorouracil based CT for mCRC as 1st- or 2nd- line therapy. The primary endpoint was to investigate the safety profile of the treatments. The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), overall survival(OS) and quality of life(QoL). RECIST 1.1 and NCI CTC AE 4.03 criteria were used to evaluate the efficiency and safety, respectively. Results The recruitment was from March 2011 to December 2013. A total of 606 patients, median age 56.6 (range, 22-81) years and 76.7% with ECOG PS (0-1), were enrolled and treated with BV plus fluorouracil based CT as 1st-line (n=453) or 2nd-line (n=153) therapy. The median cycles on BV treatment were 5.0 (3.0-8.0) cycles. Total 102 patients(16.8%) experienced grade≥3 AEs. In which grade≥3 AEs related to BV were reported in 66 patients(10.9%). AESIs defined in this study were hypertension (1.8%), proteinuria (0.8%), gastrointestinal perforation (0.5%), bleeding (3.3%), arterial thromboembolism (0.3%), colon venous thromboembolism (1.0%), fistula formation (0.8%) and wound healing complications (0.2%). The ORR was 18.3% (95%CI: 15.3%-21.6%). The ORR of 1st- and 2nd-line therapy were 21.0% (95%CI: 17.3%-25.0%) and 10.5% (95%CI: 6.1%-16.4%),respectively (P=0.0035). The median PFS(mPFS) and median OS (mOS) were 9.1 (95%CI: 8.1-9.8) and 21.9 months (95%CI: 17.1-25.7), respectively. First-line patients had similar mPFS or mOS with 2nd-line patients (P=0.6530 and 0.3695, respectively). The mPFS and mOS in the patients(treatment cycles<8) were 7.8(95%CI: 6.2-8.9) and 17.6 months (95%CI:14.9-24.8), respectively. The mPFS and mOS in patients (treatment cycles≥8) were 11.6 (95%CI:10.9-14.4) and 30.8 months (95%CI:21.3-), respectively. The mPFS and mOS in the patients (treatment cycles≥8) were longer than the patients (treatment cycles<8) (P=0.0001 and P=0.001, respectively). The mPFS were 9.8 months (95%CI: 6.7-12.3) in KRAS wild-type patients and 8.6 months(95%CI:6.2-9.9) in KRAS mutant patients (P=0.2784), respectively. The mOS were 25.7 months (95%CI:16.9-) in KRAS wild-type patients and 14.3 months (95%CI:10.3-21.9) in KRAS mutant patients (P=0.1015), respectively. Conclusion The safety profile, such as BV-related AEs in REACT study seemed well tolerated in Chinese patients and compatible with those date reported from other pivotal studies in European and America as well as Chinese registration trial. BV combined with fluorouracil based CT,is effective as observed in this trial. And the patients who received longer treatment(≥8 cycles) trend to have better treatment outcomes compared with those shorter treatment duration (<8 cycles).Thus,BV combined fluorouracil based CT worth further wide use in Chinese clinical practice.

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