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).
Gastrointestinal (Colorectal) Cancer
2017 ASCO Annual Meeting
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
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.
|Population||Median OS (95% CI)||Log-rank||Adjusted HR|
|L-sided R-sided||p-value||(95%, CI)|
|80405 (N = 728)||32.9 (30.7, 35.3) 19.6 (7.0, 23.6)||< 0.0001||1.39 (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)||0.918||0.62 (0.32, 1.23)|
|Cet (N = 96)||40.3 (34.0, 48.3) 18.4 (14.2, 30.1)||0.003||1.68 (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|