Response rate and survival for patients with metastatic colorectal cancer from right-sided versus left-sided tumors, treated with first-line triplet chemotherapy with bevacizumab.

Abstract

801 Background: Recent data have shown that right sided colonic cancer represent a molecularly different class of tumors from the left sided ones with worse survival in patients treated with doublets systemic chemotherapy. We report the result of response and survival on patients treated with triplet chemotherapy according to the primary tumor location. Methods: Medical records of patients treated with triplet chemotherapy (capecitabine, oxaliplatin and irinotecan) in combination with bevacizumab on a prospective clinical trial (clinicaltrial.gov: NCT01311050), were retrospectively reviewed for the location of primary tumor. Right sided tumors: from cecum to hepatic flexure. Left sided tumors: from splenic flexure to and including the rectum. Transverse colon were excluded. Patients who had multiple primaries were considered right sided if at least one of them was right sided. Results: Fifty-three patients treated with above triplet therapy. Eleven were right sided and 42 were left sided. Characteristics for right vs left sided tumors were as follow: Median age: 46 (range 24-55 years) vs 53 ( 32-74 years), male: 5 (46%) vs 23 (55%), performance status 0-1: 9 (82%) vs 37 (88%), KRAS wild: 3 (27) vs 12 (29%), single metastatic site: 5 (46%) vs 14 (33%) and Prior adjuvant chemotherapy: none vs 6 (14%). Response rate (complete and partial) were 6 (54%) in right sided tumors and 24(57%) in left sided tumors. Progression free and overall survival for right sided tumors was 22 (95% confidence interval (CI) 12.3-31.7) and 22 months (95% CI 16.6-27.4) and for left sided tumors were 12 (95% CI 3.5-20.5) and 28 months (95% CI 22.7-33.2) respectively. Conclusions: First-line triplet chemotherapy with bevacizumab may overcome the poor prognosis of metastatic right sided colonic cancer. Clinical trial information: NCT01311050.

Chemotherapy plus bevacizumab as an optimal first-line therapeutic treatment for patients with right-sided metastatic colon cancer: a meta-analysis of first-line clinical trials

“…Studies demonstrate a lack of consensus regarding to which kind of biological antibody is more effective to improve prognosis of patients with right-sided mCRC 22 26. In the present study, we specifically observed that survival of the right-sided patients was inferior to the left-sided individuals with first-line chemotherapy alone or chemotherapy plus bevacizumab, respectively.…”

“…The detailed search and selection procedure are depicted in figure 1. A total of 16 first-line trials,5 7 17–24 including 4574 patients with mCRC, were ultimately fulfilled the inclusion criteria. The baseline characteristics within each eligible study are summarised in table 1.…”

“…As shown in table 1, 4306 patients within 14 included trials were confirmed as unresectable mCRC cases, which composed the metastatic setting in our study. Eight trials with 3154 patients with mCRC5 7 18 19 23 24 and 10 trials including 3247 patients with mCRC5 7 17 20 22 25 reported the survival difference between the right-sided and left-sided patients receiving first-line chemotherapy alone and chemotherapy plus bevacizumab, respectively. Effects of bevacizumab within the left-sided and right-sided patients were examined in three trials 5 17.…”

“…There is significant heterogeneity in genetic alteration and tumour microecology in right-sided and left-sided cancer 35 36. High CpG island methylator phenotype and microsatellite instability as well as hypermutation within DNA mismatch repair (MMR), MAPK, TGF-β and insulin signalling pathways are prevalent in the right-sided disease compared with its counterpart 22 37–39. The MMR-deficient status impairs genomic stability, leading to carcinogenesis, chemoresistance and progression of the disease 40 41.…”