Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Introduction: Neoadjuvant immune checkpoint inhibitors (nICI) have rapidly gained attention as a promising treatment modality in head and neck cancer, with innumerable trials underway. While clinical endpoints including overall survival are traditionally utilized when incorporating novel therapeutics into treatment paradigms, they may not fully capture the short-term benefit, including improved surgical morbidity, associated with nICI. To facilitate timely expansion of candidacy for this promising modality, there is a need to identify not only meaningful surrogate endpoints for survival, but also endpoints which highlight benefit beyond survival. The purpose of this study is to evaluate surgical endpoints previously used in neoadjuvant head and neck cancer clinical trials, to inform future trial design.
Methods: A systematic review was performed to identify any neoadjuvant head and neck cancer trials that reported a surgical endpoint as a primary or secondary outcome. Both mucosal and cutaneous disease were included, and there was no restriction based on year. Outcomes of interest included surgical margin status, R0 resection rate, organ preservation rate, and surgical de-escalation. PubMed, SCOPUS, OVID, Cochrane Central, and CINAHL databases were queried. Two independent investigators reviewed each study prior to inclusion.
Results: Fourteen trials, spanning 20 years, met inclusion criteria. Four trials (28.5%) reported on the use of nICI +/- chemotherapy, and 10 trials (71.4%) reported on induction chemotherapy alone. Organ preservation rate (OPR) was reported for all induction chemotherapy trials, with rates ranging from 51.6-98.9% for locally advanced head and neck cancer. Of the 4 nICI trials, 2 (50%) reported R0 resection rate, 1 reported OPR (25%), and 1 reported a composite score based on the degree of both functional and organ preservation (25%).
Discussion: While surgical endpoints were commonly utilized in early neoadjuvant chemotherapy trials, there is a paucity of data on surgical endpoints for nICI trials. Surgical endpoints, such as R0 resection rate, may serve as appropriate surrogates for survival outcomes, however, are infrequently reported in the literature. nICI has the potential to de-escalate surgical treatment and decrease surgical morbidity, which is underemphasized in reports of nICI outcomes. This benefit can be better delineated through inclusion of surgical endpoints in future nICI trials.