Best of ASCO - 2014 Annual Meeting

 

Welcome

Attend this session at the
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

Association between gene fusions and anti-EGFR resistance signature in colorectal cancer.

Sub-category:
Advanced Disease

Category:
Gastrointestinal (Colorectal) Cancer

Meeting:
2019 ASCO Annual Meeting

Abstract No:
3564

Poster Board Number:
Poster Session (Board #56)

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 3564)

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

Abstract Disclosures

Abstract:

Background: Acquired resistance to anti-EGFR therapy in metastatic colorectal cancer (mCRC) has been characterized by a circulating tumor DNA (ctDNA) signature including any sub-clonal RAS mutation, co-existing RAS mutations, or co-existing EGFR mutations. Here, we investigated if fusions in ctDNA are associated with this anti-EGFR signature for CRC patients (pts). Methods: 4289 advanced stage CRC pts underwent molecular profiling using a plasma-based NGS assay that included FGFR2, FGFR3, RET, ALK, NTRK1, and ROS1 fusions. Available clinical histories were reviewed. Correlations between fusions and clinicopathological features were measured with a Fischer exact test. Relative frequencies of genomic alterations were compared between fusion-present vs -absent cases with an unpaired t-test. Clonality for a given alteration was called for a relative variant allele frequency (rVAF) > 50 %, while subclonal was defined as < 50% rVAF. Results: 44 unique fusions were detected in 40 (1.1%) of the 3808 pts with alterations present: RET (N = 16), FGFR3 (N = 12), ALK (N = 10), NTRK1 (N = 3), ROS1 (N = 2), and FGFR2 (N = 1). Relative to non-fusion variants detected, fusions were more likely to be subclonal (OR 8.2, p < 0.0001). Mutations associated with a previously reported anti-EGFR resistance were found in FGFR3 (7/12 pts), RET (7/15 pts) and ALK (5/10 pts). In fusion-present cases, co-existing RAS mutations were more likely to be subclonal than non-fusion cases (OR 14, p < 0.0001). EGFR mutations were more common in fusion present cases (OR 3.7, p = 0.0001) and predominantly subclonal (97%). EGFR mutations aggregated to ectodomain sites (85%) previously linked to acquired anti-EGFR resistance. For 27 pts with available clinical histories, 21 (78%) received anti-EGFR treatment prior to ctDNA testing. Conclusions: Actionable fusions using a ctDNA NGS assay were predominantly subclonal and co-existed with subclonal RAS and EGFR mutations. These clinicopathologic features are consistent with a previously validated signature linked to resistance to anti-EGFR therapies in CRC. We hypothesize that fusions may arise as a previously undescribed mechanism of acquired resistance to anti-EGFR therapies in CRC pts.

 
Other Abstracts in this Sub-Category:

 

1. Randomized phase III study comparing FOLFOX + bevacizumab versus folfoxiri + bevacizumab (BEV) as 1st line treatment in patients with metastatic colorectal cancer (mCRC) with ≥3 baseline circulating tumor cells (bCTCs).

Meeting: 2019 ASCO Annual Meeting Abstract No: 3507 First Author: Javier Sastre
Category: Gastrointestinal (Colorectal) Cancer - Advanced Disease

 

2. Updated results of TRIBE2, a phase III, randomized strategy study by GONO in the first- and second-line treatment of unresectable mCRC.

Meeting: 2019 ASCO Annual Meeting Abstract No: 3508 First Author: Chiara Cremolini
Category: Gastrointestinal (Colorectal) Cancer - Advanced Disease

 

3. A randomized phase II trial of second-line CAPTEM versus FOLFIRI in MGMT methylated, RAS mutated metastatic colorectal cancer (mCRC) patients.

Meeting: 2019 ASCO Annual Meeting Abstract No: 3509 First Author: Filippo Pietrantonio
Category: Gastrointestinal (Colorectal) Cancer - Advanced Disease

 

More...