Right-sided Primary CRC Predicts Poorer Metastatic Disease Survival

Primary tumour site may significantly influence survival for patients with metastatic colorectal cancer

medwireNews: Analysis of results from a registry and two trials suggest that metastatic colorectal cancer (CRC) patients with right-sided primary tumours have significantly poorer survival than those with left-sided disease.

“This easy-to-collect dichotomous information on side of origin could be of added value in clinical decision-making, and should be considered an important stratification factor for future randomized trials”, say Heinz-Josef Lenz, from the University of Southern California in Los Angeles, USA, and team.

“Validation of these results in adjuvant and additional metastatic studies of CRC is warranted.”

The researchers examined data for 200 patients registered in the pharmacogenetic irinotecan-based PROVETTA registry, and 559 and 1268 participants of the phase III irinotecan-based AVF2107g and oxaliplatin-based NO16966 trials, respectively. Left-sided tumours were identified in 72.0%, 63.1% and 73.7% of the patients, respectively.

The PROVETTA study showed that patients with left-sided tumours were significantly less likely to have BRAF Mutations than patients with right-sided tumours, regardless of mucinous histology.

Moreover, left-sided tumours were associated with significantly longer median overall survival (OS) at 42.0 versus 24.8 months (hazard ratio [HR]=0.44) and progression-free survival (PFS) at 12.1 versus 9.9 months (HR=0.52).

Multivariate analysis confirmed that tumour side and BRAF status were significantly predictive of OS, the researchers write in the Journal of the National Cancer Institute.

The protective effects of left-sided tumours were also demonstrated in the AVF2107g and NO16966 trials, with significant HRs for longer OS of 0.55 and 0.71, respectively.

Contrary to earlier results, tumour side did not significantly predict response to bevacizumab.

But Howard Hochester, from Yale Cancer Center in New Haven, Connecticut, USA, suggests in an accompanying editorial that the greater treatment effect on right-sided CRC with oxaliplatin compared with irinotecan may shed light on the surprising relative lack of benefit for adjuvant bevacizumab in the NO16966 versus the AVF2107g trials.

“The present report provides an apparent explanation, as the data demonstrate a greater benefit of oxaliplatin-based chemotherapy overall and a disproportionate effect on the right-sided colon lesions, reducing the relative bevacizumab benefit”, he summarises.

“We see here, that oxaliplatin may be more effective than irinotecan for right-sided metastatic colon cancer and that bevacizumab further narrows the gap by differential treatment effect for lesions originating in the right side of the colon.”

References

Loupakis F, Yang D, Yau L, et al.  Primary Tumor Location as a Prognostic Factor in Metastatic Colorectal Cancer.  J Natl Cancer Inst 2015; Advance online publication 25 February. doi: 10.1093/jnci/dju427

Hochester HS. The bipartisan colon. J Natl Cancer Inst 2015; Advance online publication 25 February. doi: 10.1093/jnci/djv011

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