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- Title
Prognostic and Predictive Impact of Primary Tumor Sidedness for Previously Untreated Advanced Colorectal Cancer.
- Authors
Yin, Jun; Cohen, Romain; Jin, Zhaohui; Liu, Heshan; Pederson, Levi; Adams, Richard; Grothey, Axel; Maughan, Timothy S; Venook, Alan; Cutsem, Eric Van; Punt, Cornelis; Koopman, Miriam; Falcone, Alfredo; Tebbutt, Niall C; Seymour, Matthew T; Bokemeyer, Carsten; Rubio, Eduardo Diaz; Kaplan, Richard; Heinemann, Volker; Chibaudel, Benoist
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
COLORECTAL cancer; PROGNOSIS; OVERALL survival; TREATMENT effectiveness; PROGRESSION-free survival
- Publication
JNCI: Journal of the National Cancer Institute, 2021, Vol 113, Issue 12, p1705
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/djab112