Hypertension as a predictor of outcome and treatment response to cetuximab: A retrospective analysis of NCIC CTG CO.17.

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Session Type and Session Title: 
Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Abstract Number: 


Poster Board Number: 
Poster Session B Board #D2
J Clin Oncol 34, 2016 (suppl 4S; abstr 256)
Shelly Sud, Christopher J. O'Callaghan, Caleb Jonker, Christos Stelios Karapetis, Timothy Jay Price, Niall C. Tebbutt, Jeremy David Shapiro, Guy A. Van Hazel, Nick Pavlakis, Peter Gibbs, Mark Jeffery, Lillian L. Siu, Sharlene Gill, Ralph Wong, Derek J. Jonker, Dongsheng Tu, Rachel Anne Goodwin; Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada; NCIC Clinical Trials Group, Kingston, ON, Canada; Ottawa Hospital Cancer Centre, Ottawa, ON, Canada; Flinders Medical Centre and Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, Australia; Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia; Austin Health, Melbourne, Australia; Department of Medical Oncology, Victoria, Australia; University of Western Australia, Perth, Australia; Department of Medical Oncology, Royal North Shore Hospital, The University of Sydney, Sydney, Australia; Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Christchurch Hospital, Christchurch, New Zealand; Princess Margaret Cancer Centre, Toronto, ON, Canada; BC Cancer Agency, Vancouver, BC, Canada; CancerCare Manitoba, Winnipeg, MB, Canada; NCIC CTG, The Ottawa Hospital, Ottawa, ON, Canada

Abstract Disclosures


Background: Adrenergic receptor stimulation is involved in development of hypertension (HTN), and is implicated in progression and dissemination of metastases in tumour types such as colon cancer (CRC). Adrenergic antagonists, such as beta-blockers (BB), demonstrate inhibition of invasion and migration in CRC cell lines and have been associated with decreased mortality in advanced CRC. We examined the association of baseline HTN (BHTN) and use of BB on overall (OS) or progression-free survival (PFS) of pts with pre-treated, chemotherapy refractory, metastatic CRC (mCRC). We also examined BHTN and BB use as predictors of Cetuximab (CET) efficacy. Methods: Using data from NCIC CO.17 (CET vs. BSC), we coded BHTN and use of anti-HTN meds (Rx), including BB, for 572 pts. Chi-square test assessed association between these variables and baseline characteristics. Univariate and multivariate analyses of OS and PFS by BHTN diagnosis and BB use were performed using Cox regression models. Results: Pts with BHTN (149/572) and those using BB (60/572) were older, had diminished performance status, and higher creatinine levels. BHTN, BB use and anti-HTN Rx were not prognostic for OS and PFS, though a trend was noted between BB use and improved PFS (HR 1.38 [0.97- 1.96], p= 0.077). BHTN and BB use were not significant predictors of CET benefit. However, pts with BHTN tended to have a stronger treatment effect in PFS from CET (interaction p = 0.074). Conclusions: In chemo-refractory mCRC, BHTN and BB use are not significant prognostic factors. BHTN and BB use are also not predictive of CET benefit, though pts with baseline HTN may benefit from a stronger treatment effect with CET. Patients with chemo-refractory mCRC may be biologically selected and the impact of BB use in earlier lines may therefore still warrant investigation.

Interaction between factor and treatment
Hazard ratio
(CET vs. BSC)
(95% CI)
[p value]
Hazard ratio
(95% CI)
[p value]
Overall survivalHypertensive pts0.67 (0.45-0.98)
1.20 (0.77-1.86)
Non-hypertensive pts0.77 (0.62 -0.95)
Progression-free survivalHypertensive pts0.49 (0.34-0.69)
1.43 (0.97-2.11)
Non-hypertensive pts0.75 (0.62-0.92)