Prognostic and Predictive Impact of Primary Tumor Sidedness for Previously Untreated Advanced Colorectal Cancer
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Prognostic and Predictive Impact of Primary Tumor Sidedness for Previously Untreated Advanced Colorectal Cancer. / Yin, Jun; Cohen, Romain; Jin, Zhaohui; Liu, Heshan; Pederson, Levi; Adams, Richard; Grothey, Axel; Maughan, Timothy S; Venook, Alan; Van Cutsem, Eric; Punt, Cornelis; Koopman, Miriam; Falcone, Alfredo; Tebbutt, Niall C; Seymour, Matthew T; Bokemeyer, Carsten; Rubio, Eduardo Diaz; Kaplan, Richard; Heinemann, Volker; Chibaudel, Benoist; Yoshino, Takayuki; Zalcberg, John; Andre, Thierry; De Gramont, Aimery; Shi, Qian; Lenz, Heinz-Josef.
In: JNCI-J NATL CANCER I, Vol. 113, No. 12, 29.11.2021, p. 1705-1713.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Prognostic and Predictive Impact of Primary Tumor Sidedness for Previously Untreated Advanced Colorectal Cancer
AU - Yin, Jun
AU - Cohen, Romain
AU - Jin, Zhaohui
AU - Liu, Heshan
AU - Pederson, Levi
AU - Adams, Richard
AU - Grothey, Axel
AU - Maughan, Timothy S
AU - Venook, Alan
AU - Van Cutsem, Eric
AU - Punt, Cornelis
AU - Koopman, Miriam
AU - Falcone, Alfredo
AU - Tebbutt, Niall C
AU - Seymour, Matthew T
AU - Bokemeyer, Carsten
AU - Rubio, Eduardo Diaz
AU - Kaplan, Richard
AU - Heinemann, Volker
AU - Chibaudel, Benoist
AU - Yoshino, Takayuki
AU - Zalcberg, John
AU - Andre, Thierry
AU - De Gramont, Aimery
AU - Shi, Qian
AU - Lenz, Heinz-Josef
N1 - © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
PY - 2021/11/29
Y1 - 2021/11/29
N2 - BACKGROUND: Unplanned subgroup analyses from several studies have suggested primary tumor sidedness (PTS) as a potential prognostic and predictive parameter in metastatic colorectal cancer (mCRC). We aimed to investigate the impact of PTS on outcomes of mCRC patients.METHODS: PTS data of 9277 mCRC patients from 12 first-line randomized trials in the ARCAD database were pooled. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for age, sex, performance status, prior radiation/chemotherapy, and stratified by treatment arm. Predictive value was tested by interaction term between PTS and treatment (cetuximab plus chemotherapy vs chemotherapy alone). All statistical tests were 2-sided.RESULTS: Compared with right-sided metastatic colorectal cancer patients (n = 2421, 26.1%), left-sided metastatic colorectal cancer patients (n = 6856, 73.9%) had better OS (median = 21.6 vs 15.9 months; adjusted hazard ratio [HRadj] = 0.71, 95% confidence interval [CI] = 0.67 to 0.76; P < .001) and PFS (median = 8.6 vs 7.5 months; HRadj = 0.80, 95% CI = 0.75 to 0.84; P < .001). Interaction between PTS and KRAS mutation was statistically significant (Pinteraction < .001); left-sidedness was associated with better prognosis among KRAS wild-type (WT) (OS HRadj = 0.59, 95% CI = 0.53 to 0.66; PFS HRadj =0.68, 95% CI = 0.61 to 0.75) but not among KRAS mutated tumors. Among KRAS-WT tumors, survival benefit from anti-EGFR was confirmed for left-sidedness (OS HRadj = 0.85, 95% CI = 0.75 to 0.97; P = .01; PFS HRadj = 0.77, 95% CI = 0.67 to 0.88; P < .001) but not for right-sidedness.CONCLUSIONS: The prognostic value of PTS is restricted to the KRAS-WT population. PTS is predictive of anti-EGFR efficacy, with a statistically significant improvement of survival for left-sidedness mCRC patients. These results suggest treatment choice in mCRC should be based on both PTS and KRAS status.
AB - BACKGROUND: Unplanned subgroup analyses from several studies have suggested primary tumor sidedness (PTS) as a potential prognostic and predictive parameter in metastatic colorectal cancer (mCRC). We aimed to investigate the impact of PTS on outcomes of mCRC patients.METHODS: PTS data of 9277 mCRC patients from 12 first-line randomized trials in the ARCAD database were pooled. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for age, sex, performance status, prior radiation/chemotherapy, and stratified by treatment arm. Predictive value was tested by interaction term between PTS and treatment (cetuximab plus chemotherapy vs chemotherapy alone). All statistical tests were 2-sided.RESULTS: Compared with right-sided metastatic colorectal cancer patients (n = 2421, 26.1%), left-sided metastatic colorectal cancer patients (n = 6856, 73.9%) had better OS (median = 21.6 vs 15.9 months; adjusted hazard ratio [HRadj] = 0.71, 95% confidence interval [CI] = 0.67 to 0.76; P < .001) and PFS (median = 8.6 vs 7.5 months; HRadj = 0.80, 95% CI = 0.75 to 0.84; P < .001). Interaction between PTS and KRAS mutation was statistically significant (Pinteraction < .001); left-sidedness was associated with better prognosis among KRAS wild-type (WT) (OS HRadj = 0.59, 95% CI = 0.53 to 0.66; PFS HRadj =0.68, 95% CI = 0.61 to 0.75) but not among KRAS mutated tumors. Among KRAS-WT tumors, survival benefit from anti-EGFR was confirmed for left-sidedness (OS HRadj = 0.85, 95% CI = 0.75 to 0.97; P = .01; PFS HRadj = 0.77, 95% CI = 0.67 to 0.88; P < .001) but not for right-sidedness.CONCLUSIONS: The prognostic value of PTS is restricted to the KRAS-WT population. PTS is predictive of anti-EGFR efficacy, with a statistically significant improvement of survival for left-sidedness mCRC patients. These results suggest treatment choice in mCRC should be based on both PTS and KRAS status.
U2 - 10.1093/jnci/djab112
DO - 10.1093/jnci/djab112
M3 - SCORING: Journal article
C2 - 34061178
VL - 113
SP - 1705
EP - 1713
JO - JNCI-J NATL CANCER I
JF - JNCI-J NATL CANCER I
SN - 0027-8874
IS - 12
ER -
