Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
IMPORTANCE: Neoadjuvant immunotherapy has shown promising results in melanoma, in both upfront response and overall prognosis. Its role in head and neck cancers (HNC) remains unknown. The theoretical synergistic effect of cytotoxic chemotherapy and immune checkpoint inhibitors makes chemoimmunotherapy regimens particularly promising. Multiple recent trials in HNC have evaluated both immunotherapy and chemoimmunotherapy neoadjuvant regimens.
OBJECTIVE: To summarize and compare the efficacy of neoadjuvant immunotherapy and chemoimmunotherapy regimens in locoregionally advanced resectable HNC.
DATA SOURCES: We conducted a librarian-led systematic review using multiple electronic databases including Ovid MEDLINE(R), Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
STUDY SELECTION: Inclusion criteria included randomized and nonrandomized prospective interventional trials that have completed accrual, with results published in English. Only trials reporting pathologic response and/or response evaluation criteria in solid tumors (RECIST) response were included. Retrospective studies or trials that did not include immune checkpoint inhibitors were excluded. Trials investigating nonresectable disease or disease that was not treatment naïve were excluded as well.
DATA EXTRACTION AND SYNTHESIS: Two investigators (H.B. and C.H.) independently conducted title, abstract, and full text review per PRISMA guidelines. Primary outcomes extracted from included studies were: Major (MPR, defined as residual tumor) and Complete Pathologic Response (CPR) at surgery and Complete Response (CR) on imaging by RECIST 1.1. Secondary outcomes collected included 1-year overall survival (OS) and toxicity.
MAIN OUTCOME(S) AND MEASURE(S): A meta-analysis was performed using a binary random effects model to determine the pooled proportion of the primary outcomes in the immunotherapy and chemoimmunotherapy groups. Heterogeneity among studies was reported as I2.
RESULTS: Of 411 articles identified in the systematic review, 250 were excluded on title review and 138 were excluded on abstract review. A total of 749 patients across 23 studies were included in the meta-analysis, with 355 (47%) patients across 13 studies undergoing chemoimmunotherapy, 102 (14%) patients across 5 studies undergoing dual immunotherapy, and 292 (39%) patients across 10 studies undergoing single agent immunotherapy. The pooled rates of MPR/CPR were 6.2/2.6% (p=.53, I2=.0007/p=.97, I2=0) across studies assessing single agent immunotherapy, compared to 18/4.6% (p=.001, I2=0.65/ p=.99, I2=0.0) across studies assessing dual immunotherapy, and 66/38% (p=.002, I2=.59/p=.027, I2=0.463) across studies assessing chemoimmunotherapy. The pooled rates of CR by RECIST criteria were 12% (p=.077, I2=0.42) for chemoimmunotherapy, while both single and dual immunotherapy reported no cases of CR. 1 year OS rates were high among patients receiving single agent immunotherapy (88-96%), dual immunotherapy (88-96%), and chemoimmunotherapy (88-100%). In 19 studies reporting adverse events, grade 3-5 toxicities were reported in 16% of patients.
CONCLUSIONS AND RELEVANCE: Neoadjuvant immunotherapy and chemoimmunotherapy regimens are well tolerated in HNC. Pathologic and radiographic response rates using chemoimmunotherapy regimens are higher than dual or single agent neoadjuvant immunotherapy regimens. Radiographic response appears to underpredict eventual pathologic response across regimens. Early oncologic outcomes after neoadjuvant chemoimmunotherapy are encouraging, but longer follow-up is needed to identify a lasting survival advantage.