Effect of neoadjuvant immunotherapy and targeted therapies on surgical resection in patients with solid tumors: A systematic review and meta-analysis.

511 Background: Neoadjuvant immunotherapy with anti-programmed cell death protein-1 (PD-1) or anti-programmed cell death ligand-1 (PD-L1) and tyrosine kinase inhibitor (TKI) therapy is currently being used to treat certain solid tumours prior to surgery. Neoadjuvant therapy may cause delays to resection potentially losing a window of opportunity. We explored the pooled proportion of patients with solid tumours receiving neoadjuvant therapy who completed planned surgical resection. Methods: Medline, CENTRAL and Embase databases were searched for single arm or randomized controlled trials studying neoadjuvant PD-1/PD-L1 immunotherapy or TKI therapy. Random-effects model was used to estimate the pooled proportion of patients undergoing planned resection, and weights were estimated using inverse variance method. Statistical heterogeneity was calculated using the I 2 and chi-squared test. Results: From 368 relevant articles, eleven studies with a total of 382 patients receiving neoadjuvant PD-1 immunotherapy (n = 234) or neoadjuvant TKI therapy (n = 148) were analyzed. The types of tumours included hepatocellular carcinoma (1 study), renal cell carcinoma (8 studies), bladder carcinoma (1 study) or non-small cell lung cancer (1 study). The pooled proportion of patients who completed planned surgery after neoadjuvant therapy was 95% (95% CI 0.92 to 0.99). The overall partial response rate prior to surgery was 12% (95% CI 0.07 to 0.16) in the PD-1 therapy group and 46% (95% CI -0.12 to 1.03) in the TKI group. The pooled serious adverse events rate was 17% (95% CI 0.02 to 0.32) in the PD-1 therapy group and 29% (95% CI -0.10 to 0.68) in the TKI group. For all patients receiving neoadjuvant therapy, the pooled median overall survival was 23.41 months (95% CI 16.21 to 30.62) and median progression free survival was 7.46 months (95% CI 4.41 to 10.51). Conclusions: Neoadjuvant PD-1 or TKI therapy prior to surgery for solid tumours is safe, does not delay surgical resection and can result in a partial radiological response prior to surgery.