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E-Poster Display

459P - Effect of RAS amplification (RASa) on outcomes to EGFR monoclonal antibody therapy (EGFRmAb) in metastatic colorectal cancer (mCRC)

Date

17 Sep 2020

Session

E-Poster Display

Topics

Immunotherapy

Tumour Site

Colon and Rectal Cancer

Presenters

Marwan Fakih

Citation

Annals of Oncology (2020) 31 (suppl_4): S409-S461. 10.1016/annonc/annonc270

Authors

M. Fakih1, J. Lee2, J.S. Sandhu1, R. Madison2, J. Venstrom2, B. Alexander3, A.B. Schrock2

Author affiliations

  • 1 Medical Oncology And Therapeutics Research, City of Hope, 91010 - Duarte/US
  • 2 Clinical Development, Foundation Medicine, 02210 - Boston/US
  • 3 Radiation Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, 02115 - Boston/US

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Abstract 459P

Background

RAS mutations (RASm) in CRC are associated with lack of benefit from EGFRmAb. However, the effect of RASa on outcome and response to EGFRmAb in CRC patients (pts) remains ill-defined.

Methods

Clinical outcomes were assessed independently in (1) The City of Hope (COH) single institution cohort of 338 CRC pts with FM comprehensive genomic profiling (CGP), (2) the Flatiron Health-Foundation Medicine (FM) clinico-genomic database (CGDB), a nationwide de-identified EHR-derived DB linked to CGP data of 3,904 mCRC pts as of 12/31/19. Time to therapy discontinuation (TTD) and overall survival (OS) were estimated with Kaplan-Meier analysis and adjusted/unadjusted (age at dx, therapy line, practice type) hazard ratios (HR/aHR) from Cox models. Genomic analysis utilized the FM GDB of 37,233 CRCs.

Results

In the COH cohort, 6 pts with RASa alone (13-54 copies) received EGFRmAb post-CGP; 4/6 had progressive disease and 2 had stable disease, with median TTD 2.5 mos. In the CGDB, median TTD was shorter in pts with RASa alone (n = 9; 4.7 vs. 7.6 mos; HR: 1.4 [0.70-2.8]; aHR: 1.2 [0.60-2.4]) and RASm (n = 101; 5.3 vs. 7.6 mos; HR: 1.5 [1.2-1.9]; aHR: 1.6 [1.3-2.0]) compared to RAS/BRAF V600E wild-type (WT) pts (n = 608). Similarly, median OS was shorter in RASa alone (11.4 vs. 13.7 mos; HR: 1.6 [0.75-3.4]; aHR: 1.6 [0.77-3.4]) and RASm (9.4 vs. 13.7 mos; HR: 1.5 [1.1-1.9]; aHR: 1.5 [1.1-2.0]) vs WT pts. EGFRmAb was combined with chemotherapy in 6/6 (COH) and 8/9 (CGDB) pts and distributed across 1st-4th lines. In the FM GDB RASa was detected in 1.6% (614/37,233) of CRCs. RASa 6-9 (n=241, 39%), 10-19 (n=165, 27%) and ≥20 copy (n=209, 34%) subsets had co-RASm/BRAF V600E in 63%/3%, 31%/0.6% and 4.8%/0% of cases, respectively. P<0.01 for all co-RASm comparisons.

Conclusions

mCRC pts with RASa alone (1.1% of CRC) may have lower TTD and OS on EGFRmAb compared to RAS/BRAF WT pts, although the differences here were not statistically significant. Combination chemotherapy likely also confounds potential negative impact of EGFRmAb monotherapy. Larger independent studies are warranted to determine if RASa, including degree of copy gain, may be an additional negative biomarker for selection of EGFRmAb in mCRC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Foundation Medicine.

Funding

Foundation Medicine.

Disclosure

M. Fakih: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Array; Advisory/Consultancy: Bayer; Speaker Bureau/Expert testimony: Guardant; Research grant/Funding (institution): Astra Zeneca; Research grant/Funding (institution): Novartis. J. Lee: Full/Part-time employment: Foundation Medicine; Shareholder/Stockholder/Stock options: Roche. R. Madison: Full/Part-time employment: Foundation Medicine ; Shareholder/Stockholder/Stock options: Roche. J. Venstrom: Leadership role, Travel/Accommodation/Expenses, Full/Part-time employment: Foundation Medicine; Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options: Roche; Advisory/Consultancy: Synkrino. B. Alexander: Leadership role, Full/Part-time employment: Foundation Medicine; Shareholder/Stockholder/Stock options: Roche; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Puma Biotechnology; Research grant/Funding (institution): Celgene. A.B. Schrock: Full/Part-time employment: Foundation Medicine; Shareholder/Stockholder/Stock options: Roche. All other authors have declared no conflicts of interest.

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