Abstract 852P
Background
The C1 molecular subtype of HGSOC is associated with a poor prognosis and exhibits high AXL gene expression. Sensitivity to the AXL kinase inhibitor, bemcentinib (BerGenBio), has been demonstrated in-vitro for C1 subtype HGSOC (Antony et al 2018). Positive AXL expression has been associated with improved progression-free survival (PFS) in lung cancer patients treated with bemcetinib and pembrolizumab (Krebs et al SITC 2019, CT03184571). The prevalence of AXL protein expression and its prognostic value in C1 HGSOC remain undefined.
Methods
82 Archival HGSOC primary tumour samples from 30 patients were prospectively analysed using the Ovarian Tumor Tissue Analysis Consortium NanoString codeset to determine transcriptional ovarian cancer molecular subtypes. AXL immunohistochemistry (IHC) scoring using an AXL-specific antibody was performed to determine AXL protein expression. The highest AXL mRNA expression level across tumour samples from each individual patient (AXL max-mRNA) was correlated with AXL IHC and HGSOC molecular subtype. Clinical data was collected by retrospective medical record review.
Results
AXL IHC was assessable in 29/30(97%) patients. Of these, AXL+ was observed in 19/29(66%). AXL mRNA expression showed positive correlation with AXL protein expression (Spearman rho = 0.3, p = 0.005). High AXL max-mRNA expression was noted in 12/15(63%) of AXL+ cases. Amongst HGSOC subtypes, the C1 subtype was found to be enriched in samples that had both high AXL max-mRNA and AXL+ (Fisher’s exact p=0.03). The C1 subtype was found in 6/19 (31.6%) of cases who were AXL+, and 6/12(50%) of cases with both high AXL max-mRNA and AXL+. The combination of both high AXL max-mRNA and AXL+ was prognostic for first-line PFS (HR 3.7, p=0.006), and overall survival (HR 4.9, p=0.04).
Conclusions
This is the first study to demonstrate a correlation between AXL IHC, AXL mRNA expression and C1 HGSOC. The AXL IHC has potential predictive and prognostic value, and its utility as a predictive biomarker for C1 HGSOC warrants further exploration in AXL targeted trials.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
BerGenBio, NMRC/CTGIITE/0004/2016.
Disclosure
N.Y.L. Ngoi: Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): Johnson & Johnson. D. Micklem, J. Nautiyal, A. Jackson, J.B. Lorens, H. Gabra: Leadership role, Full/Part-time employment: BerGenbio. L. Johnson, A. Rayford: Full/Part-time employment: BerGenBio. D.S. Tan: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer; Honoraria (self): Foundation Medicine; Honoraria (self): Janssen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self): Tessa Therapeutics; Research grant/Funding (institution): Karyopharm Therapeutics; Travel/Accommodation/Expenses: Novartis. All other authors have declared no conflicts of interest.