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Attend this session at the
2017 ASCO Annual Meeting!


Session: Gastrointestinal (Colorectal) Cancer

Type: Oral Abstract Session

Time: Monday June 5, 3:00 PM to 6:00 PM

Location: Hall D2

Primary (1°) tumor location as an independent prognostic marker from molecular features for overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB / SWOG 80405 (Alliance).

Sub-category:
Advanced Disease

Category:
Gastrointestinal (Colorectal) Cancer

Meeting:
2017 ASCO Annual Meeting

Abstract No:
3503

Citation:
J Clin Oncol 35, 2017 (suppl; abstr 3503)

Author(s): Alan P. Venook, Fang-Shu Ou, Heinz-Josef Lenz, Omar Kabbarah, Xueping Qu, Donna Niedzwiecki, Tyler Zemla, Richard M. Goldberg, Howard S. Hochster, Bert H. O'Neil, Hanna Kelly Sanoff, Robert J. Mayer, Monica M. Bertagnolli, Charles David Blanke, Federico Innocenti; University of California, San Francisco, San Francisco, CA; Mayo Clinic Cancer Center, Rochester, MN; Division of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA; Genentech, Inc., San Francisco, CA; Duke University Medical Center, Durham, NC; Mayo Clinic, Rochester, MN; Ohio State University Comprehensive Cancer Center, Columbus, OH; Yale Cancer Center, New Haven, CT; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Dana-Farber Cancer Institute/Partners CancerCare, Boston, MA; Brigham and Women's Hospital, Boston, MA; Oregon Health & Science University, Portland, OR; The University of North Carolina at Chapel Hill, Chapel Hill, NC

Abstract Disclosures

Abstract:

Background: 80405 found no OS or Progression Free Survival (PFS) difference when bevacizumab (BV) or cetuximab (Cet) was added to 1st-line FOLFOX or FOLFIRI in All RAS wild type (wt) mCRC pts. There was a significant 1° side by biologic interaction (P int: OS = 0.008, PFS = 0.001) favoring pts with left-sided (L) 1°. Analyses of 1° tumors beyond All RAS includes Consensus Molecular Subtype (CMS), BRAF and MSI. (CMS results - see Lenz et al; BRAF -see Innocenti et al) We asked whether 1° tumor location - L vs right (R) - is an independent prognostic marker when these other molecular features are considered. Methods: We used a Cox proportional hazard model stratified by prior XRT and +/- adjuvant chemo; adjusted for age, gender, synchronous vs metachronous, CMS, MSI and BRAF status. Pts with transverse (T) tumors were excluded in this analysis. Results: Sidedness was determined in 782 pts (L - 472; R - 256; T -54). Molecular data from 728 pts (with L - and R-sided 1°s) was available as follows: KRAS -- 291, NRAS -393, BRAF - 393, MSI - 378, CMS - 533. L vs R mOS: 32.9 v 19.6 months (mo) (p < 0.0001). See Table for OS results in All RAS / BRAF wt and BRAF mutant (mut) pts. Sidedness (R vs L) is an independent prognostic marker even after adjusting for all these molecular features: HR = 1.392 (1.032, 1.878), p = 0.031. Conclusions: Primary tumor location is an independent prognostic factor when adjusted for age, gender, synchronous/metachronous, CMS, MSI and BRAF status. We are exploring clinical variables such as tumor burden, metastatic sites and measurability of disease in an attempt to explain the impact of sidedness. Support: U10CA188021, U10CA180882. Eli Lilly and Co, Genentech/Roche, Pfizer, Sanofi.Clinical trial information: NCT002655850.

PopulationMedian OS (95% CI)Log-rankAdjusted HR
L-sided R-sidedp-value(95%, CI)
80405 (N = 728)32.9 (30.7, 35.3) 19.6 (7.0, 23.6)< 0.00011.39 (1.03, 1.88)
All RAS /BRAF wt (N = 225)
BV (N = 91)38.7 (34.3, 42.3) 34.4 (23.6, 82.0)0.9180.62 (0.32, 1.23)
Cet (N = 96)40.3 (34.0, 48.3) 18.4 (14.2, 30.1)0.0031.68 (0.85, 3.34)
BRAF mut (N = 48)
BV (N = 23)12.0 (4.8, 14.5) 23.7 (7.9, 36.9)0.035
Cet (N = 16)9.6 (8.6, NE) 5.8 (1.9, 11.7)0.508

 
Other Abstracts in this Sub-Category:

 

1. Final DFS results of the SCOT study: An international phase III randomised (1:1) non-inferiority trial comparing 3 versus 6 months of oxaliplatin based adjuvant chemotherapy for colorectal cancer.

Meeting: 2017 ASCO Annual Meeting Abstract No: 3502 First Author: Timothy Iveson
Category: Gastrointestinal (Colorectal) Cancer - Advanced Disease

 

2. Somatic DNA mutations, MSI status, mutational load (ML): Association with overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC) of CALGB/SWOG 80405 (Alliance).

Meeting: 2017 ASCO Annual Meeting Abstract No: 3504 First Author: Federico Innocenti
Category: Gastrointestinal (Colorectal) Cancer - Advanced Disease

 

3. Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG S1406).

Meeting: 2017 ASCO Annual Meeting Abstract No: 3505 First Author: Scott Kopetz
Category: Gastrointestinal (Colorectal) Cancer - Advanced Disease

 

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