MMP-9/ANC score as a predictive biomarker for efficacy of bevacizumab plus platinum doublet chemotherapy in patients with advanced or recurrent non-squamous non-small cell lung cancer

Subtitle:

Article type: Research Article

Authors: Hiura, Kazuya^{a; b} | Shiraishi, Akiko^a | Suzuki, Chinami^c | Takamura, Kei^d | Yamamoto, Makoto^d | Komori, Hitoshi^e | Watanabe, Yasuhiro^a | Iwaki-Egawa, Sachiko^{a; *}

Affiliations: [a] Division of Life Science, Hokkaido Pharmaceutical University School of Pharmacy, Sapporo, Japan | [b] Department of Hospital Pharmacy, Abashiri Kosei General Hospital, Abashiri, Japan | [c] Department of Hospital Pharmacy, Engaru Kosei General Hospital, Engaru, Japan | [d] First Department of Internal Medicine, Obihiro Kosei General Hospital, Obihiro, Japan | [e] Department of Hospital Pharmacy, Obihiro Kosei General Hospital, Obihiro, Japan

Correspondence: [*] Corresponding author: Sachiko Iwaki-Egawa, Division of Life Science, Hokkaido Pharmaceutical University, School of Pharmacy, 7-15-4-1 Maeda, Teine, Sapporo 006-8590, Hokkaido, Japan. Tel.: +81 11 676 8700; Fax: +81 11 676 8666; E-mail: sachiko@hokuyakudai.ac.jp

Abstract: BACKGROUND: Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), which is a key regulator of tumor angiogenesis. OBJECTIVE: To evaluate biomarkers to predict the benefit of paclitaxel and carboplatin plus bevacizumab (PCB) therapy in patients with advanced or recurrent non-squamous non-small cell lung cancer. METHODS: Among 21 patients treated with PCB, 10 were included in the good responder group and 11 in the non-responder group. Serum VEGF, MMP-2 and MMP-9 were measured using ELISA. RESULTS: There were no significant differences in these markers levels between groups. However, the good responder group showed a significantly higher pre-treatment MMP-9/ absolute neutrophil count (ANC) score than the non-responder group before the treatment (p= 0.014), and there was a positive correlation between the score and the tumor reduction rate (r= 0.57, p= 0.016). Furthermore, by dividing patients into a high scoring group (MMP-9/ANC ≥ median, n= 11) and a low scoring group (MMP-9/ANC < median, n= 10), former group showed a significant improvement in the median progression-free survival compared with latter group (636 vs. 196 days, p = 0.032). CONCLUSIONS: MMP-9/ANC score before PCB treatment may be a suitable biomarker to assess the anti-tumor effects of PCB therapy.

Keywords: Absolute neutrophil count, matrix metalloproteinase-9, progression-free survival, tumor reduction rate, VEGF

DOI: 10.3233/CBM-150483

Journal: Cancer Biomarkers, vol. 15, no. 4, pp. 433-440, 2015