Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Proffered Paper 2 – Gastrointestinal tumours, colorectal

4878 - Next-generation sequencing (NGS) in metastatic colorectal cancer (mCRC): novel mutated genes and their effect on response to therapy (Alliance)


30 Sep 2019


Proffered Paper 2 – Gastrointestinal tumours, colorectal


Tumour Site

Colon and Rectal Cancer


Federico Innocenti


Annals of Oncology (2019) 30 (suppl_5): v198-v252. 10.1093/annonc/mdz246


F. Innocenti1, N. Rashid2, M. Wancen2, F. Ou3, X. Qu4, S. Denning5, M. Bertagnolli6, C.D. Blanke7, A. Venook8, O. kabbarah9, H.J. Lenz10

Author affiliations

  • 1 Dpet, University of North Carolina, 27599 - Chapel Hill/US
  • 2 Lineberger Comprehensive Cancer Center, University of North Carolina, 27517 - Chapel Hill/US
  • 3 Medical Oncology Department, Mayo Clinic, 55905 - Rochester/US
  • 4 Oncology Biomarkers Development, Genentech, 94080 - South San Francisco/US
  • 5 Division Of Pharmacotherapy And Experimental Therapeutics, University of North Carolina, 27514 - Chapel Hill/US
  • 6 Surgical Oncology, Brigham and Women's Hospital, 2115 - Boston/US
  • 7 Center For Health And Healing, Oregon Health Science University, 97239 - Portland/US
  • 8 Cancer Treatment Center, UCSF Helen Diller Family Comprehensive Cancer Center, 94115 - San Francisco/US
  • 9 Cancer Biology, ORIC Pharmaceuticals, 94080 - San Francisco/US
  • 10 Medical Oncology, USC - Norris Comprehensive Cancer Center, 90033 - Los Angeles/US


Login to get immediate access to this content.

If you do not have an ESMO account, please create one for free.

Abstract 4878


CALGB (Alliance)/SWOG 80405 was a randomized phase III trial that found no difference in overall survival (OS) in first-line mCRC Patients (pts) treated with bevacizumab (Bev) or cetuximab (Cet) combined with the same chemotherapy. By applying NGS to tumour DNA collected from pts in the trial, we aimed to discover novel mutated genes associated with differential response to therapy with the biologics and prognosis.


Primary tumour DNA from 520 pts was profiled for somatic gene mutations. Mutations in 426 genes were determined by NGS (FoundationOne). OS was the primary endpoint, both as a time-to-event and a categorical (<20 or ≥ 20 months) variable. Cox proportional hazard models (hazard ratio, HR) and logistic regression (odds ratio, OR) were used, respectively, adjusted by MSI status, BRAF V600E, all RAS mutations, arm, gender, and age. Interactions between mutated genes and treatment (Bev versus Cet) on OS were tested.


In Bev-treated pts, tumours with mutated IGF1 (6%) conferred worse OS than WT tumours (HR 2.8 [1.5-5.2], p = 0.0009), and tumours with mutated KDR (11%) conferred worse OS than WT tumours (OR 4.4 [1.6-12.3], p = 0.004). In Cet-treated pts, tumours with mutated FANCD2 (6%) conferred worse OS than WT tumours (HR 2.7 [1.4-5.3], p = 0.004), and tumours with mutated APC (74%) conferred better OS than WT tumours (OR 0.3 [0.1-0.6], p = 0.0009). RNF43-mutated tumours (12%) and SMARCA4-mutated tumours (6%) conferred worse OS in Cet-treated pts than Bev-treated pts (interaction p-value 0.002 and 0.0009, respectively). In all patients in the study, FANCI-mutated tumours (4%) conferred worse OS than WT tumours (HR 2.0 [1.2-3.3], p = 0.005; OR 5.0 [1.9-14.8], p = 0.002). The full set of NGS results will be presented, including the mutational map of tumour location.


To our knowledge, this is the largest and most comprehensive NGS analysis of somatic DNA mutations in tumours from mCRC pts treated with standard of care therapy. It provides novel gene candidates affecting response to Bev and Cet, each combined with chemotherapy, as well as mutated genes affecting the prognosis of patients. If validated in other phase III studies, these results may be used to guide treatment decisions in pts with mCRC.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study

The authors.


U10CA180821, U10CA180882, U10CA180888 and U10CA180830 (SWOG); Genentech, Eli Lilly & Co., Pfizer, Sanofi.


X. Qu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech. M. Bertagnolli: Research grant / Funding (self): BMS; Research grant / Funding (self): Eli Lilly; Research grant / Funding (self): Roche; Research grant / Funding (self): Sanofi; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Genentech. A. Venook: Research grant / Funding (self), travel: Genentech; Research grant / Funding (self): BMS; Travel / Accommodation / Expenses: Roche. O. Kabbarah: Full / Part-time employment: Genentech; Shareholder / Stockholder / Stock options: Roche. H.J. Lenz: Honoraria (self): Roche; Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.