Right- and left-sided colorectal cancers respond differently to cetuximab

Abstract

IntroductionRight-sided colon cancer (RSCC) and left-sided colorectal cancer (LSCRC) differ with respect to their biology and genomic patterns. This study aimed to examine whether the primary tumor location is associated with the response to cetuximab in patients with metastatic colorectal cancer (mCRC).MethodsPatients with mCRC treated with cetuximab and standard chemotherapy as first- or second-line treatments were compared with randomly chosen patients who were treated with chemotherapy alone between 2005 and 2013. The main outcome measures were the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The differences in the outcome were analyzed by using the chi-squared test, Student’s t test, and Kaplan-Meier method.ResultsThe treatment results of 206 patients with mCRC treated with cetuximab and standard chemotherapy as first- or second-line treatments were compared with those of 210 patients who were treated with chemotherapy alone. As a first-line treatment, cetuximab with chemotherapy was associated with a significantly higher ORR (49.4 % vs. 28.6 %, P = 0.005) as well as longer PFS (9.1 vs. 6.2 months, P = 0.002) and OS (28.9 vs. 20.1 months, P = 0.036) than chemotherapy alone in patients with LSCRC. However, cetuximab neither improved the ORR (36.4 % vs. 26.2 %, P = 0.349) nor prolonged PFS (5.6 vs. 5.7 months, P = 0.904) or OS (25.1 vs. 19.8 months, P = 0.553) in patients with RSCC. As a second-line treatment, cetuximab exhibited a tendency to improve the ORR (23.5 % vs. 10.2 %, P = 0.087) and prolong PFS (4.9 vs. 3.5 months, P = 0.064), and it significantly prolonged OS (17.1 vs. 12.4 months, P = 0.047) compared with chemotherapy alone in the patients with LSCRC. In contrast, as a second-line treatment, cetuximab neither improved the ORR (7.1 % vs. 11.4 %, P = 0.698) nor prolonged PFS (3.3 vs. 4.2 months, P = 0.761) or OS (13.4 vs. 13.0 months, P = 0.652) in patients with RSCC.ConclusionsThe addition of cetuximab to chemotherapy in both first- and second-line treatments of mCRC may only benefit patients with primary LSCRC.

Comparison of survival between right‐sided and left‐sided colon cancer in different situations

“…Unmeasured factors in SEER database, such as chemotherapy and tumor biology, including MSI status might play roles in patient outcome. Recent reports showed that RSCC and LSCC even had different response to the anti‐Epidermal growth factor receptor (EGFR) and anti‐Vascular endothelial growth factor (VEGF) monoclonal antibody . We could not fully evaluate the impact of chemotherapy and target therapy on survival of RSCC and LSCC patients.…”

PIK3CA Mutations Contribute to Acquired Cetuximab Resistance in Patients with Metastatic Colorectal Cancer

“…Right-sided colon cancers have embryologic origin in the midgut and have higher rates of microsatellite instability, gene promoter hypermethylation leading to gene silencing, and BRAF mutation, whereas left-sided tumors originate from the hindgut and have a genomic profile distinct from right-sided tumors. Recently, many studies(2–4) demonstrated that the predictive value of the location was mainly related to the response to biologic agents, cetuximab and bevacizumab, of which, cell proliferation and developmental pathways such as RAF/RAS/ERK/MEK and mTOR/PI3K/AKT pathways could play vital roles in response to anti-EGFR antibody, cetuximab.…”

Chemotherapy plus bevacizumab versus chemotherapy plus cetuximab as first-line treatment for patients with metastatic colorectal cancer

“…[6–10] While mutations in the RAS oncogene well predicts resistance to anti-EGFR agents, [11–14] however, no biomarker can predict the magnitude of benefit from bevacizumab or cetuximab in the RAS wild-type population so far. [15–17] Their optimal use in terms of patient selection, drug combinations, and regimen sequences remains inconclusive. [18–21] …”