P37.19 Activin-A and GDF-11 as Predictive Biomarkers for Platinum Response in Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer death in Australia with 13,000 new cases per year. Although targeted therapy and immunotherapy have drastically changed the treatment landscape, the majority of patients will receive platinum-based chemotherapy for which the response rate is approximately 30% (Reck et al, 2016). An immunohistochemistry-based, predictive biomarker would be beneficial for patients and help avoid toxicity for patients unlikely to respond. 3 potential biomarkers identified in a paper by Marini et al (2018) – activin A, growth differentiation factor-11 (GDF-11) and transforming growth factor-b (TGF-B) –were investigated in a real-world retrospective cohort to determine their relation to objective radiological response and overall survival (Marini et al, 2018). We identified 101 patients with advanced non-small cell lung cancer who received platinum chemotherapy at 2 cancer centres between 2014-2015. Archival formalin-fixed paraffin embedded tissue samples were stained with activin A and GDF-11. Slides were manually scored by 2 independent clinicians including a specialist pathologist using the multiplicative quickscore method, which multiplies the percentage of tumour cells and intensity staining of 0-3+ to create a score out of 18 (Detre et al, 1995). We performed Kaplan Meier analysis and a Cox-proportional hazards model for confounding variables using R software to analyse the relationship between high immunohistochemistry scores (greater than the median score) and overall survival. A chi square analysis was performed to analyse the relationship between immunohistochemistry expression and objective radiological response. We performed statistical analysis around the median cytoplasmic score for Activin-A (6) and GDF-11 (12). The overall median survival was 15.3 months. No significant difference in survival was detected between the two populations for Activin-A (p value = 0.97) or GDF-11 (p=0.67). The immunohistochemistry score was also not associated with rates of partial response for Activin A (p value = 0.98) or GDF-11 (p=0.56). Rates of progressive disease were also not associated with high levels of expression of Activin-A (p value 0.22) or GDF-11 (p=0.12). Despite an association with lower progression-free survival in a retrospective cohort in a previous study, high expression of activin and GDF-11 does not appear to predict for platinum response or overall survival in the setting of non-small cell lung cancer. Further research into TGF-B is in progress.