ESMO 2018 Congress | OncologyPRO

Abstract 5146

Background

EGFR amp occurs in 6-10% of gastroesophageal adenocarcinomas (OGA). The effect of EGFR amp on survival in advanced chemotherapy treated OGA is unknown. We evaluated EGFR amp in tissue and plasma in patients (pts) treated in the REAL3 trial.

Methods

REAL3 was a randomised, open-label phase 3 trial in treatment naïve, advanced OGA pts assessing the addition of panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOX) (HR 1.37 (95% CI 1.07-1.76) p = 0.013; EOX-P vs EOX). DNA was extracted from pre-treatment biopsies and plasma. EGFR copy number was assessed by ddPCR using probes for EGFR and reference probe CNTNAP2 (Ch7). EGFR:CNTNAP2 copy number assessment allowed detection of EGFR amp and exclusion of Ch7 polysomy. The association between EGFR amp and progression free and overall survival (PFS/OS) was assessed by the Kaplan-Meier method and Cox regression.

Results

271 pts (of a total 553 pts treated) had tissue analysed. EGFR ratio was ≥2 in 19/271 (7.0%); 14/271 (5.2%) had ratio ≥5. Plasma was analysed in 370 pts; 23/370 (6.2%) had EGFR ratio ≥2 and 10/370 (2.7%) had ratio ≥5. EGFR amp pts were balanced according to clinicopathological variables. Of 14 EGFR amp tissue samples 7 plasma samples (50%) were concordant; all had EGFR ratio ≥ 5. OS and PFS by EGFR amp are shown in the table. Results were similar for ratio ≥5. Multivariate analysis adjusted for age, gender, PS and histology demonstrated a similar prognostic trend in each arm.Table: 646P

OS and PFS by arm and EGFR amp

EOX OS
	EGFR	n	Median OS (95% C.I.)	HR (95% C.I.)
Tissue	<2	120	12.5 (9.5-15.7)	Ref
	≥2	7	11.5 (na)	1.2 (0.5-2.8)
Plasma	<2	163	11.8 (10.5-14.6)	Ref
	≥2	4	11.5 (na)	1.6 (0.5-5.0)
EOX PFS
Tissue	<2	120	7.6 (6.4-8.9)	Ref
	≥2	7	6.6 (na)	1.4 (0.6-3.2)
Plasma	<2	163	7.1 (6.2-8.6)	Ref
	≥2	4	6.5(na)	1.2 (0.4-3.2)
EOX-P OS
Tissue	<2	113	8.5 (7.0-9.7)	Ref
	≥2	10	5.7 (1.7-12.9)	1.3 (0.7-2.4)
Plasma	<2	169	9.7 (8.5-11.8)	Ref
	≥2	18	7.8 (3.9-12.9)	1.6 (0.8-3.1)
EOX-P PFS
Tissue	<2	113	5.7 (4.5-6.3)	Ref
	≥2	10	2.7 (1.6-12.2)	1.2 (0.6-2.3)
Plasma	<2	169	6.9 (6.0-8.6)	Ref
	≥2	18	5.3 (2.6-10.0)	1.28 (0.8-2.1)

Conclusions

Liquid biopsy using ddPCR can detect EGFR amp in advanced OGA patients; higher levels of EGFR tissue amp may predict plasma status. EGFR amp appears to be negatively prognostic, however due to low biomarker prevalence this difference was not significant.

Clinical trial identification

NCT00824785.

Legal entity responsible for the study

Royal Marsden.

Funding

Royal Marsden National Institute for Health Research Biomedical Research Centre.

Editorial Acknowledgement

Disclosure

E. Smyth: Honoraria for advisory role: Servier, BMS, Five Prime Therapeutics, Gritstone Oncology, Celgene. D. Cunningham: Research funding (Inst): Amgen, AstraZeneca, Bayer, Celgene, MedImmune, Merck Serono, Merrimack, Sanofi. S. Rao: Honoraria: Shire Pharmaceuticals, Celgene, Lilly, Amgen, BMS; Travel/accommodation: Celgene, Amgen, Bayer. T.S. Waddell: Honoraria: BMS, Pfizer, Ipsen, Roche. A. Okines: Honoraria (speakers fee): Roche. T. Crosby: Honoraria for advisory role: Lilly. W. Mansoor, J. Wadsley: Honoraria: Novartis, Merck; Travel/accommodation: Ipsen, Merck. G. Middleton: Research funding: Kael-Gemvax. I. Chau: Honoraria: Amgen, Gilead Sciences, Lilly, Pfizer, Taiho Pharmaceutical; Consulting, Advisory role: Bayer, Bristol-Myers Squibb, Five Prime Therapeutics, Lilly, MSD Oncology, Roche/Genentech, Sanofi; Research funding (Inst): Janssen-Cilag, Lilly, Merck Serono, Sanofi; Travel, accommodations, expenses: Bristol-Myers Squibb, Lilly, Merck Serono, MSD, Sanofi. N. Valeri: Honoraria: Bayer, Merck, Eli Lilly. All other authors have declared no conflicts of interest.

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

5146 - EGFR amplification (amp) and survival in the REAL-3 trial

Date

Session

Topics

Tumour Site

Presenters

Citation

Authors

Author affiliations

Resources

Abstract 5146

Background

Methods

Results

Conclusions

Clinical trial identification

Legal entity responsible for the study

Funding

Editorial Acknowledgement

Disclosure

Abstract 5146

Background

Methods

Results

Conclusions

Clinical trial identification

Legal entity responsible for the study

Funding

Editorial Acknowledgement

Disclosure

Resources from the same session