Left Versus Right: Does Location Matter for Refractory Metastatic Colorectal Cancer Patients in Phase 1 Clinical Trials?
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Location of the primary tumor is prognostic and predictive of efficacy with VEGF-inhibitors (I) versus EGFR-I given first-line to metastatic colorectal cancer (mCRC) patients. However, little is known regarding the effect of location on prognosis and prediction in refractory mCRC. We assessed the efficacy of VEGF-I and EGFR-I in regards to location of the primary tumor in patients with refractory mCRC enrolled in early phase studies.
A historical cohort analysis of mCRC patients, including 44 phase I trials our institution, from March 2004 to September 2012. Median Progression free survival (mPFS) and overall survival (mOS) were estimated from Kaplan-Meier curves and groups were statistically compared with the log-rank test.
One hundred thirty-nine patients with a median age 59 (33–81). 73.9% received 3+ lines of therapy. All KRAS wild-type patients had received prior EGFR-I. Location: right 20.9%, left 61.9%, and transverse 4.3%. For survival analysis, transverse CRC were included with right. Of the 112 patients, mOS was left (N = 80) 6.6 months versus right (N = 32) 5.9 months, P = 0.18. mPFS was left (n = 86) 2.0 months versus right (N = 35) 2.0 months, P = 0.76. In subgroup analysis, survival was significant for KRAS wild-type patients with left-sided mCRC had mOS of 6.2 months with other agents versus 9.4 months with EGFR-I (P = 0.03).
In phase 1 clinical trials, although location alone was not prognostic in heavily pretreated patients, left-sided mCRC had improved survival with EGFR-I. Despite progression on EGFR-I, left-sided KRAS wild mCRC patients should be considered for phase 1 studies of agents targeting growth factor pathways.
KeywordsColorectal cancer Early phase clinical trials Location EGFR inhibitors
NCI P30CA054174 (All Authors), NIA P30AG044271 (Sukeshi Patel Arora).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
P30 Cancer Center Support Grant No. CA054174 (all authors), NIA P30AG044271 (Sukeshi Patel Arora).
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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