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2019 ASCO Annual Meeting!

Session: Gastrointestinal (Colorectal) Cancer

Type: Poster Session

Time: Monday June 3, 8:00 AM to 11:00 AM

Location: Hall A

Identifying anti-EGFR (EGFRi) response subgroups using evidence of ctDNA selective pressure.


Gastrointestinal (Colorectal) Cancer

2019 ASCO Annual Meeting

Abstract No:

Poster Board Number:
Poster Session (Board #79)

J Clin Oncol 37, 2019 (suppl; abstr 3587)

Author(s): Christine Megerdichian Parseghian, Jason Willis, Van K. Morris, Kanwal Pratap Singh Raghav, Arvind Dasari, Victoria M. Raymond, Richard B. Lanman, Michael J. Overman, Scott Kopetz; University of Texas MD Anderson Cancer Center, Houston, TX; The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; Guardant Health, Inc., Redwood City, CA; UT MD Anderson Cancer Center, Houston, TX

Abstract Disclosures


Background: Metastatic colorectal cancers (mCRC) that respond to EGFRi display a robust circulating tumor DNA (ctDNA) signature that reflects selective pressure and clonal evolution. Conversely, non-responding tumors do not exhibit this signature. On this basis, we developed a novel method that defines EGFRi sensitivity with improved biological confidence with fewer patients (pts), and does not rely on clinical trial outcomes where responses may be confounded by concurrent chemotherapy. We used this method to further elucidate the association of several features that have been previously reported to be associated with EGFRi resistance, namely tumor sidedness, BRAF, PIK3CA, or ERBB2 (HER2) MTs, and the absence of APC/TP53MT. Methods: We analyzed 112 pts with baseline tissue based RASWT mCRC who had progressed following EGFRi, and with plasma samples available for ctDNA sequencing using a blood based NGS assay. Using our previously validated EGFRi exposure signature, we identified pts with evidence of selective pressure. Results: Post EGFRi ctDNA found 37% and 33% of pts with left sided and transverse tumors displayed evidence of selective pressure, respectively. 0 pts with right sided tumors displayed evidence of selective pressure; p= 0.01. Similarly, BRAFV600EMT displayed no evidence of selective pressure vs 30% of WT pts; in contrast, selective pressure was evident in pts with PIK3CAMT, ERBB2MT and pts with absence of APC/TP53MT (42% vs 28%, 67% vs 28%, 24% vs 43%, respectively for MT vs WT, p= NS for all). BRAF, PIK3CA, ERBB2, and APC/TP53 MT were present in 4/117, 12/108, 3/118 and 30/91 pts, respectively. ctDNA shedding was similar for all subgroups, as was time from previous EGFRi, indicating that these factors were not confounders. Conclusions: Consistent with prior large randomized studies, no pts with right sided tumors or BRAFMT had evidence of biologic benefit as assessed by presence of selective pressure. In contrast a number of pts with transverse tumors, ERBB2MT, PIK3CAMT or absence of APC/TP53MT had evidence of EGFR selective pressure, confirming that these are not absolute predictors of EGFR resistance and suggesting a subset of these pts were deriving benefit from EGFR inhibition. This biology based approach has the potential to more efficiently evaluate biomarkers of targeted therapy in the future without reliance on large randomized datasets.

Other Abstracts in this Sub-Category:


1. Association of colon cancer (CC) molecular signatures with prognosis and oxaliplatin prediction-benefit in the MOSAIC Trial (Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer).

Meeting: 2019 ASCO Annual Meeting Abstract No: 3503 First Author: Katherine L. Pogue-Geile
Category: Gastrointestinal (Colorectal) Cancer - Biomarkers/Epidemiology/Outcomes


2. A pooled analysis of multicenter cohort studies of post-surgery circulating tumor DNA (ctDNA) in early stage colorectal cancer (CRC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 3518 First Author: Jeanne Tie
Category: Gastrointestinal (Colorectal) Cancer - Biomarkers/Epidemiology/Outcomes


3. Relative contribution of clinical and molecular features to outcome within low and high risk T and N groups in stage III colon cancer (CC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 3520 First Author: Frank A. Sinicrope
Category: Gastrointestinal (Colorectal) Cancer - Biomarkers/Epidemiology/Outcomes