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Poster display session

3248 - Circulating levels of ADAM12, a stromal activation biomarker, are predictive of survival in pancreatic ductal adenocarcinoma (PDAC)

Date

09 Sep 2017

Session

Poster display session

Presenters

Hanneke van Laarhoven

Citation

Annals of Oncology (2017) 28 (suppl_5): v209-v268. 10.1093/annonc/mdx369

Authors

H.W.M. van Laarhoven1, H. Damhofer2, V.L. Veenstra2, C. Waasdorp2, L.B. van Rijssen3, F. Dijk4, J.W. Wilmink5, M.G. Besselink3, O.R. Busch3, J.P. Medema2, J. Shiansong Li6, R. Jiang6, D.W. Pierce7, M.F. Bijlsma8

Author affiliations

  • 1 Department Of Medical Oncology, Academic Medical Center (AMC), 1105AZ - Amsterdam/NL
  • 2 Laboratory For Experimental Oncology And Radiobiology, Center Of Experimental And Molecular Medicine, Academic Medical Center (AMC), Amsterdam/NL
  • 3 Department Of Surgery, Academic Medical Center (AMC), Amsterdam/NL
  • 4 Department Of Pathology, Academic Medical Center (AMC), Amsterdam/NL
  • 5 Department Of Medical Oncology, Academic Medical Center (AMC), Amsterdam/NL
  • 6 Biostatistics, Celgene Corporation, 07901 - Summit/US
  • 7 Translational Medicine, Celgene Corporation, 07901 - Summit/US
  • 8 Laboratory For Experimental Oncology And Radiobiology, Center Of Experimental And Molecular Medicine, Academic Medical Center (AMC), 1105AZ - Amsterdam/NL
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Abstract 3248

Background

The dense stroma of PDAC promotes tumor growth and impedes delivery of cytotoxic drugs. We assessed the utility of ADAM12, a circulating biomarker of PDAC stroma identified in our preclinical models, to non-invasively measure stromal activation in patients (pts) and predict outcomes.

Methods

The prognostic and predictive value of ADAM12 was determined in an institutional cohort from the Academic Medical Center (AMC), which included 144 pts with PDAC (58 resected and 86 non-resected pts) and 38 non-age–matched healthy controls, and in a cohort of 372 pts with metastatic PDAC treated with nab-paclitaxel plus gemcitabine (nab-P/Gem) or Gem alone in the MPACT trial.

Results

For the AMC cohort, higher serum ADAM12 levels (median, 372 pg/mL; P < .01) were found in pts with PDAC vs healthy controls (median, 154 pg/mL). High ADAM12 levels (> median) were significantly associated with poor survival (P = .04) in resected pts but not in non-resected pts (P = .67). In the pooled MPACT analysis, median overall survival (OS) was significantly longer (9.3 vs 6.9 months; log-rank P = .01) in pts with no detectable (ND; n = 95) vs detectable (n = 277) serum ADAM12 levels at baseline (BL). Median OS was longer in pts with ADAM12 decrease (fold change [FC] < 1) vs increase (FC > 1) from BL to cycle 2, but both OS values were significantly shorter than that in pts with ND ADAM12 levels at either time point (Table). In a multivariate analysis, baseline ADAM12 levels (0 vs > 0; P = .02), treatment (nab-P/Gem vs Gem; P = .02), and Karnofsky performance status (90-100 vs 70-80; P < .01) were significant predictors of OS. Table. OS in pts with ADAM12 measured at both BL and cycle 2 in the MPACT studyTable:

745P

Overall Populationnab-P/Gem ArmGem Arm
Deaths, n/N (%)Median OS (95% CI), moDeaths, n/N (%)Median OS (95% CI), moDeaths, n/N (%)Median OS (95% CI), mo
FC  154/58 (93)8.1 (6.5 - 9.9)25/27 (93)8.3 (6.5 - 11.3)29/31 (94)6.9 (5.5 - 9.3)
ND30/38 (79)13.2 (9.3 - 16.4)17/22 (77)14.4 (8.5 - 19.2)13/16 (81)12.0 (6.8 - 14.9)
HR (95% CI); P value
FC  1 vs ND FC  11.5 (1.0 - 2.3); < .05 2.3 (1.4 - 3.6); < .01 0.7 (0.5 - 0.9); .021.8 (1.0 - 3.2); .04 2.8 (1.5 - 5.4); < .01 0.6 (0.4 - 1.0); .071.3 (0.7 - 2.3); .48 1.7 (0.9 - 3.3); .11 0.7 (0.5 - 1.2); .19

BL, baseline; FC, fold change; HR, hazard ratio; nab-P/Gem, nab-paclitaxel plus gemcitabine; ND, no detectable; OS, overall survival; pt, patient.

Conclusions

Low serum levels of ADAM12 at baseline were associated with longer OS in pts with PDAC, as were decreases in ADAM12 during treatment. ADAM12 may be a valuable biomarker to predict long-term outcomes in pts treated with nab-P/Gem.

Clinical trial identification

N/A

Legal entity responsible for the study

Celgene Corporation

Funding

Celgene Corporation

Disclosure

H.W. van Laarhoven: Advisory role, Lilly, Nordic. Research funding to institution: Bayer, BMS, Celgene, Lilly, MDS, Nordic, Roche. J.P. Medema: Employment (family member) Sanofi, Abbott/Abbvie; stock ownership (family member), Sanofi; advisory role, Bionovion; patents, royalties, other IP, Aduro Biotech. J. Shiansong Li, R. Jiang, D.W. Pierce: Employment, stock ownership, Celgene. M.F. Bijlsma: Research funding, Celgene; travel & accommodations, Biouniversa. All other authors have declared no conflicts of interest.

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