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Poster Display session 3

2512 - AXL expression predicts poor prognosis and lack of efficacy of anti-angiogenic and anti-epidermal growth factor receptor (EGFR) agents in patients (pts) with RAS wild type (WT) metastatic colorectal cancer (mCRC)

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Translational Research

Tumour Site

Presenters

Claudia Cardone

Citation

Annals of Oncology (2019) 30 (suppl_5): v25-v54. 10.1093/annonc/mdz239

Authors

C. Cardone1, B. Blauensteiner2, V. Moreno-Viedma2, P.P. Vitiello1, G. Martini1, D. Ciardiello1, V. Simeon3, A.M. Rachiglio4, D. Rizzi5, E. Maiello6, T. Latiano6, C. Cremolini7, G. Argiles Martinez8, E. Elez8, A. Falcone7, J. Tabernero8, N. Normanno4, M. Sibilia2, F. Ciardiello1, E. Martinelli1

Author affiliations

  • 1 Medical Oncology, Università degli Studi della Campania Luigi Vanvitelli, 80131 - Napoli/IT
  • 2 Department Of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, 1090 - Austria/AT
  • 3 Medical Statistics Unit, Università degli Studi della Campania Luigi Vanvitelli, 80131 - Napoli/IT
  • 4 Cell Biology And Biotherapy Unit, National Cancer Institute ‘Fondazione Giovanni Pascale’, 80100 - Napoli/IT
  • 5 Trial Office, Bari, Italy, GOIM, Bari/IT
  • 6 Medical Oncology, Ospedale Casa Sollievo della Sofferenza, 71013 - San Giovanni Rotondo/IT
  • 7 Department Of Translational Research And New Technologies In Medicine And Surgery, Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, 56126 - Pisa/IT
  • 8 Medical Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES

Resources

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Abstract 2512

Background

Activation of AXL receptor tyrosine kinase is a key mediator of epithelial to mesenchymal transition (EMT). AXL is overexpressed in several human cancers, including CRC.

Methods

AXL expression was assessed by immunohistochemistry in tumor samples from 346 mCRC pts treated at three Institutions and enrolled in different clinical trials (CAPRI, MACBETH, MOMA, TRIBE2). In silico data of AXL RNA levels were obtained from GSE5851 dataset, including 80 pts with advanced mCRC treated with cetuximab in a later line.

Results

AXL expression was found in 18% of cases within tumor cells, with no difference among RAS cohorts. In the RAS WT group, AXL positive pts had a worse mPFS whether treated with chemotherapy (CT) + anti-EGFR [6.2 m (CI95% 4.2- 8.2) vs 12.1 m (CI95% 10.6 – 13.6) p 0.012] or CT+anti-angiogenic agent [6.7 m (CI95% 8.9- 19.3) vs 14.1 m (CI95% 9.4– 13.0) p 0.007], whereas in RAS mutant pts no impact on PFS was observed. AXL expression correlated with worse mOS in both cohorts; notably, in RAS WT pts mOS was 19.9 m (CI95% 10.5- 29.2) vs 37.6 m (CI95% 31.1– 44.1) p 0.006]. In tumor stroma, assessable in 334 samples, AXL was expressed in 80% of cases, with no difference among RAS groups. AXL expression correlated with lower mOS in both cohorts. (Table) Intriguingly, AXL expression in tumor and stroma (+/+) correlated with shorter mOS; in particular, RAS WT pts (+/+) had a mOS of 19.9 m (CI95% 8.0- 31.7) vs (-/-) 50.1 m (CI95% 43.9- 56.2) p 0.004]. In silico analyses showed high AXL RNA levels in 50% of pts. Moreover, in this population treated with cetuximab, in the KRAS exon2 WT cohort (N = 43) AXL high pts had worse mPFS [1.9 m (CI95% 1.7 -2.0) vs 3.8 m (CI95% 0.7-6.7) p 0.59].Table: 121P

CohortAXL expression in tumor cellsAXL expression in stroma
NNegative <1% (%)Positive ≥1% (%)PFS months p valueOS months p valueNNegative <1% (%)Positive ≥1% (%)PFS months p valueOS months p value
Overall population346285 (82)61 (18)10.7 vs 8.0 0.00832.4 vs 23.0 0.00733466 (20)268 (80)10.7 vs 8.0 0.1141.1 vs 28.5 0.004
RAS WT (overall)175147 (84)28 (16)12.3 vs 6.6 <0.00037.6 vs 19.9 0.00616733 (20)134 (80)15.0 vs 10.7 0.03449.8 vs 33.5 0.031
RAS WT CT + anti-EGFR136114 (84)22 (16)12.1 vs 6.2 0.01235.8 vs 23.0 0.08712918 (14)111 (86)14.3 vs 10.4 0.3744.4 vs 33.5 0.11
RAS WT CT + anti-angiogenic3933 (85)6 (15)14.1 vs 6.7 0.00744.8 vs 13.2 0.0043815 (39)23 (61)15.0 vs 11.0 0.1250.1 vs 40.6 0.17
RAS mut (overall) CT + anti-angiogenic171138 (81)33 (19)9.6 vs 8.9 0.7827.6 vs 23.7 0.3316733 (20)134 (80)9.7 vs 9.2 0.9835.5 vs 24.7 0.056

Conclusions

AXL expression in tumor and stroma might have a negative prognostic relevance in mCRC. In RAS WT pts, AXL expression might represent a predictive biomarker of lack of efficacy for both anti-EGFR and anti-angiogenic agents.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Department of Precision Medicine, Università degli Studi della Campania "Luigi Vanvitelli".

Funding

AIRC MFAG-2015-ID: 7778.

Disclosure

F. Ciardiello: Advisory / Consultancy, Advisory Board: Merck KgA, Bayer, Amgen, Roche, Servier, Pfizer. E. Martinelli: Advisory / Consultancy: Merck KgA, Amgen, Bayer, Roche, Sanofi, Servier. All other authors have declared no conflicts of interest.

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