In metastatic colorectal cancer (mCRC), treatment in the first-line setting is very important to achieve longest survival.
Combination chemotherapy, FOLFOX or FOLFIRI regimes, are the backbone for mCRC treatment.
Biologic agents (anti-VEGR, anti-EGFR) were developed and used together with chemotherapy to improve survival.
- The first successful trial was combining bevacizumab with FOLFIRI, yielding around 5 months increase in survival (H Hurwitz, 2004).
- In 2009, CRYSTAL phase 3 trial with cetuximab (anti-EGFR) were publish, showing improvement of survival also, albeit around 2 months only.
Lately, more analysis were done using data from previously conducted clinical trials to understand if laterality (left-sided, right-sided) of metastatic colorectal cancer affect survival, especially with concomitant use of biologic agents (anti-EGFR, anti-VEGF).
Laterality of Colorectal Cancer
The right-sided CRC are tumours from cecum, ascending colon, hepatic flexure, and transverse colon.
The left-sided CRC are tumours from splenic flexure, descending colon, sigmoid, and rectum.
Majority of the CRC are left-sided.
The prognosis for stage IV/ mCRC was better for left-sided primary tumours than right-sided primary tumor (JM Loree, 2018).
However, for early stage I and II colorectal cancer, a population-based Surveillance, Epidemiology and End Results (SEER) analysis showed that prognosis was slightly better for right-sided CRC in term of overall survival and cancer-specific survival. Stage III CRC showed similar prognosis for both left-sided CRC and right-sided CRC (R Warschkow, 2016).
Addition of biologic agents (anti-EGFR, anti-VEGF)
In stage IV/ mCRC, addition of biologic therapy is able to improve average/ median overall survival, especially in patients with left-sided metastatic CRC.
Treatment with an anti-EGFR antibody in first-line setting left-sided mCRC leads to a significantly longer median OS compared with patients treated with bevacizumab, whereas in patient with right-sided mCRC, there is no or only a minor difference between patients treated with bevacizumab or cetuximab.
It is important to check RAS mutation status early in metastatic colorectal cancer (mCRC).
Anti-EGFR can ONLY be used is there is NO RAS mutation (RAS WT/ wild type)
The use of anti-EGFR together with chemotherapy in first-line setting improve overall survival.