Predictive biomarkers to ramucirumab in Asian metastatic gastric cancer patients: Circulating angiogenic factors of VEGFR2 and neurophilin are predictive to ramucirumab efficacy in Asian recurrent/metastatic gastric cancer patients

Background

We conducted an exploratory study to identify potential biomarkers to predict therapeutic effect of ramucirumab in combination with paclitaxel as a second line treatment for recurrent/metastatic Korean gastric cancer (GC) patients.

Methods

We retrospectively reviewed clinical efficacay and toxicity in 70 GC patients who received ramucirumab with weekly paclitaxel in an open-label expanded access program after failure to first line chemotherapy. To find potential biomarker of ramucirumab, we investigated the association between efficacy of ramucirumab and tissue molecular characteristics (EBV, MMR, HER2, EGFR, C-MET etc.). Also, we measured circulating biomarkers (VEGF, sVEGFR2, HGF, neuropillin-1, IL-8, and PIGF,) by ELISA method before and after treatment in a subset of patients (n = 44 vs. n = 14, respectively).

Results

With the median follow up of 5.3 months (range 0.5 ∼ 10.5 months), the median progression free survival (PFS) was 4.1 months (95% CI, 3.3 ∼ 4.9 months), and median overall survival (OS) was not reached. Of the 55 evaluable patients, the overall response rate (ORR) was 14.5% (8 partial responses), and disease control rate was 74.5%. Although there was no difference in PFS, OS or ORR according to receptor status, higher DCR was found in patients with EGFR high expression tumors (2 + ∼3+) compared with low expression tumors (0 ∼ 1+) (87.5% vs. 50%, p = 0.02). Regarding circulating biomarkers related to angiogenesis, longer PFS was seen in patients with higher level of pretreatment serum VEGFR2 (4.1 vs. 2.4 months; p = 0.01) and lower level of pretreatment serum neuropillin-1 (5.8 vs. 2.4 months; p 

Conclusions

Current study suggested that circulating biomarkers related to angiogenesis quantified by ELISA method may predict prolonged response to ramucirumab in the treatment of gastric cancer patient.

Clinical trial identification

Legal entity responsible for the study

N/A

Funding

N/A

Disclosure

S.Y. Rha: Consulting or advisory role in 2years: Merck & Co.Inc. Speakers' Bureau in 2 years: Novartis, Eli Lilly, Merck. All other authors have declared no conflicts of interest.