Impact of neoadjuvant immunotherapy or targeted therapies on surgical resection in patients with solid tumours: a systematic review and meta-analysis

Background: Tyrosine kinase inhibitor (TKI) therapy, antiprogrammed cell death protein-1 (PD-1) or anti-programmed cell death ligand-1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or a combination PD-1(L1)/CTLA-4 therapy in the neoadjuvant setting are currently being used to treat several solid tumours. There are concerns about the safety profile of neoadjuvant immunotherapy and subsequently, possible delays to surgery. This review summarizes the pooled proportion of patients who underwent surgery following neoadjuvant therapy and the proportion of adverse events. Methods: Medline, Central and Embase databases were searched for single-arm or randomized controlled trials studying neoadjuvant TKI, PD-1/L1 or CTLA-4 immunotherapy up until January 2021. The pooled proportion of patients who completed planned resection and the pooled proportion of adverse events were estimated using random-effects model. The inverse variance method was used to estimate weighting of each trial. Statistical heterogeneity was calculated using the I2 and χ2 test. Results: Seventeen relevant studies with a total of 535 patients were included for analysis. This included those receiving neoadjuvant neoadjuvant TKI therapy (n = 148), PD-1/L1 immunotherapy (n = 234) or combination PD-1/CLTA-4 (n = 153). The types of tumours in the included studies were renal cell carcinoma (8 studies), bladder carcinoma (3 studies), non-small cell lung cancer (3 studies), hepatocellular carcinoma (2 studies) and colon cancer (1 study). The pooled proportion of patients who completed planned surgery was 94% (95% confidence interval [CI] 0.910.97). The pooled rate of clinically relevant grade 3 or 4 adverse events reported after neoadjuvant therapy was 23% (95% CI 0.14-0.32). The incidence of partial radiologic response after neoadjuvant therapy was 22% (95% CI 0.04-0.40). Conclusion: The use of either neoadjuvant TKI, PD-1/ L1 or PD-1(L1)/CTLA-4 combination therapy before surgery for solid tumours rarely delays surgical resection, presents an adequate safety profile and can lead to partial radiologic response for some patients.