TY - JOUR
T1 - Left Versus Right
T2 - Does Location Matter for Refractory Metastatic Colorectal Cancer Patients in Phase 1 Clinical Trials?
AU - Arora, Sukeshi Patel
AU - Ketchum, Norma S.
AU - Michalek, Joel
AU - Gelfond, Jonathon
AU - Mahalingam, Devalingam
N1 - Funding Information:
NCI P30CA054174 (All Authors), NIA P30AG044271 (Sukeshi Patel Arora). The authors declare that they have no conflict of interest. P30 Cancer Center Support Grant No. CA054174 (all authors), NIA P30AG044271 (Sukeshi Patel Arora).
Publisher Copyright:
© 2017, Springer Science+Business Media New York.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Purpose: 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. Methods: 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. Results: 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). Conclusions: 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.
AB - Purpose: 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. Methods: 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. Results: 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). Conclusions: 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.
KW - Colorectal cancer
KW - EGFR inhibitors
KW - Early phase clinical trials
KW - Location
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U2 - 10.1007/s12029-017-9948-3
DO - 10.1007/s12029-017-9948-3
M3 - Article
C2 - 28432610
AN - SCOPUS:85018815380
SN - 1941-6628
VL - 49
SP - 283
EP - 287
JO - Journal of Gastrointestinal Cancer
JF - Journal of Gastrointestinal Cancer
IS - 3
ER -