Neoadjuvant PD-1/PD-L1 Inhibitors for Resectable Head and Neck Cancer

Abstract

Objective: To assess the efficacy and safety of neoadjuvant immunotherapy for resectable HNSCC. Data Sources and Study Selection: Electronic databases; PubMed (MEDLINE), EMBASE, the Cochrane Library and clinicaltrials.gov were systematically searched for published and ongoing cohort studies and randomized controlled trials for evaluating neoadjuvant immunotherapy for resectable HNSCC, the search results generated studies from 2015 to July 2021. Data Extraction and Synthesis: Two investigators independently identified and extracted articles for potential inclusion. Random and fixed models were used to achieve pooled odds ratios. All results are presented with 95% confidence intervals (CI). Data quality was assessed by means of the Cochrane Collaboration's Risk of Bias Tool. Main Outcomes and Measures: The primary outcomes were efficacy, evaluated by major pathological response (MPR) and pathological complete response (pCR) in the primary tumors and lymph nodes separately, and safety, assessed by preoperative grade 3-4 treatment related adverse events (TRAEs) and surgical delay rate. Results: A total 344 patients from 10 studies were included. In 8 studies neoadjuvant immunotherapy only was administered, and the other 2 studies combined immunotherapy with neoadjuvant chemo/radiotherapy. The overall MPR rate in the primary tumors from studies reporting on neoadjuvant immunotherapy only, was 9.7% (95%CI 3-18.9%) and the pCR was 2.9% (95%CI 0-9.5%). Preoperative G3-4 TRAEs were reported at a rate of 8.4% (95%CI 0.2-23.2%) and surgical delay at a rate of 0% (95%CI 0-0.9%). There was a favorable effect of neoadjuvant immunotherapy for all outcome measures. The subgroup analyses did not find one specific anti-PD-1/PD-L1 agent to be superior to another, and the favorable effect was demonstrated by either immunotherapy alone or in combination with anti- CTLA-4. Conclusion and Relevance: Neoadjuvant anti-PD-1/PD-L1 immunotherapy for resectable HNSCC is well tolerated and may confer therapeutic advantages implied by histopathological response. Long term outcomes are awaited.