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Anti-EGFR antibodies may get benefit as first-line treatment in metastatic right-sided colon cancer
Background
Location of the primary tumor can be prognostic and predictive of response to EGFR inhibitors as first-line treatment in mCRC suggesting that cetuximab and panitumumab confer little benefit for right side mCRC. HER2 has signaling kinase receptor as EGFR and has been successfully targeted in breast cancer and now showing activity in colon cancer.
Methods
125 metatstatic unresectable colon cancer with good PS, 71 males and 54 females with median age 35.7 years ± 15.9. Kras/Nras/Braf mutation was assessed by qPCR while VEGF and Her2 expression were assessed by IHC on primary tumors. Patients received first-line FOLFOX or XELOX plus bevacizumab.
Results
79 (63.2%) patients with right sided while 46 (36.8%) patients with left sided mCRC. Wild Kras/Nras/Braf detected in 24 (30.3%) of right sided and 12 (26%) of left sided tumors. Positive Her2 expression (score +3) found in 15 (18.9%) of right sided and seven (15.2%) of left sided tumors. Positive VEGF receptor (score +3) was presented in 60 (75.9%) of right sided and 28 (62%) of left sided tumors. After first-line chemotherapy plus bevacizumab; 55 (69.6%) out of 79 right sided achieved (CR and/or PR) versus 18 (39.1%) out of 46 left sided tumors (P 0.02). Patients with combined wild RAS/RAF & Her2+ve &VEGF-ve presented with more liver and lung metastasis (P 0.003) and age less than 40 years (P 0.05). 13.9% of patients with right sided tumors had combined (wild RAS/RAF& Her2+ve &VEGF-ve) and showed significant poorer response to first-line anti-VEGF (P 0.01) while in left sided tumors there was no difference between patients with combined (RAS/RAF wild & Her2 +ve &VEGF -ve) patients versus others (P 0.9). After follow up of two years, right sided mCRC showed better median PFS of 32 versus 27 months for left sided tumors (p < 0.001). Also, right sided mCRC showed better median OS of 42 versus 35 months for left sided tumors (p value < 0.001). In subgroup analysis, right sided mCRC with combined RAS/RAF wild &Her2 +ve &VEGF -ve showed inferior median PFS versus others (21 versus 30 months, P 0.04). Also, right sided mCRC with combined RAS/RAF wild & Her2 +ve &VEGF -ve showed inferior median OS versus others (33 versus 40 months, P 0.01). While in left sided tumors there was no difference in PFS nor OS in patients with combined RAS/RAF wild &Her2 +ve &VEGF -ve group versus others.
Conclusions
Right sided mCRC with combined RAS/RAF wild &Her2+ve &VEGF -ve expression did not benefitted from chemotherapy plus anti-VEGF as first-line setting so, we suggest that this group of patients may benefit from chemotherapy plus anti EGFR antibodies ± Her2 target therapy in first-line setting and this could be proven in future works that could help in risk adapted therapy. The primary tumor sidedness may not the only surrogate marker for selecting first-line targeted therapy in mCRC.
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosures
All authors have declared no conflicts of interest.
