Multicenter phase II study of second-line bevacizumab plus doublet combination chemotherapy in patients with metastatic colorectal cancer progressed after upfront bevacizumab plus doublet combination chemotherapy.
BACKGROUND
To investigate the efficacy and safety of bevacizumab beyond first progression combined with doublet chemotherapy in patients with metastatic colorectal cancer.


METHODS
This multicenter phase II study included 76 patients with metastatic colorectal cancer progressed after first-line bevacizumab plus doublet chemotherapy. Study treatment consisted of second-line continuation of bevacizumab plus crossover standard doublet chemotherapy, consisting of FOLFOX, CapeOX, or FOLFIRI. Bevacizumab was administered in doses of 5 mg/kg/2-week or 7.5 mg/kg/3-week according to the schedules of the combined regimen.


RESULTS
Median progression-free survival (PFS) and overall survival (OS) was 6.5 months (95 % CI, 5.2-7.8) and 12.8 months (95 % CI, 8.8-16.9), respectively, with no significant differences according to combined doublet chemotherapy. The response rate (RR) was 17.1 % (95 % CI, 8.6-5.6) with no statistical significance between regimens (p = 0.053). The first-line RR and PFS did not affect the second-line efficacy outcomes; RR (14.0 % vs 21.2 %, p = 0.405), median PFS (5.6 vs 6.7 months, p = 0.335), and OS (15.4 vs 11.0 months, p = 0.383) were not different between previous responders and non-responders, and the median PFS (p = 0.186) and OS (p = 0.495) were not different either according to the length of first-line PFS; however, OS from the first-line chemotherapy was longer in patients with longer first-line PFS (26.4 vs 14.8 months, p = 0.010). Bevacizumab-related significant adverse events included proteinuria (1.3 %) and thromboembolism (1.3 %).


CONCLUSIONS
Bevacizumab beyond first progression could be considered a treatment strategy even in patients progressed after first-line bevacizumab plus doublet chemotherapy. Second-line efficacy outcomes did not differ according to the first-line responses.
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea.
Yong Sang
YS
Hong
Jeeyun
J
Lee
Kyu-pyo
KP
Kim
Jae-Lyun
JL
Lee
Young Suk
YS
Park
Joon Oh
JO
Park
Se Hoon
SH
Park
Sun Young
SY
Kim
Ji Yeon
JY
Baek
Jee Hyun
JH
Kim
Keun-Wook
KW
Lee
Tae-You
TY
Kim
Tae Won
TW
Kim
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D005472:Fluorouracil