Representation and outcomes for older patients in phase 3 clinical trials for metastatic and unresectable head and neck squamous cell carcinoma (HNSCC): A systematic review.

Abstract

e18021 Background: Despite older adults (age 65+) constituting the majority (~ 70%) of all patients with head and neck squamous cell carcinoma (HNSCC), a standardized approach to systemic cancer treatment for this population has not been established. The underrepresentation of older adults in clinical trials, possibly due to greater co-morbidities and declining performance status, has led to insufficient evidence-based data specific to this demographic. In this systematic review, we examined the representation and outcomes of older patients in phase 3 clinical trials for metastatic and unresectable HNSCC. Methods: We conducted a systematic literature review to identify phase 3 published studies in patients with HNSCC that were metastatic, unresectable, or not amenable to definitive treatment, such as surgery or radiation. We searched Ovid MEDLINE for studies between 1985-2024. We included any mucosal HNSCC or any unknown HNSCC primary. We excluded nasopharyngeal and cutaneous squamous cell carcinomas. Two researchers independently conducted literature screening, data extraction, and quality assessment. Results: We identified 11 eligible trials for inclusion. All studies compared one or more therapeutic interventions with chemotherapy and/or immunotherapy regimens. The median age was 60, with men representing 85.3% of the study population. Older adults (age 65+) accounted for 25% of the study population. We found no definitive trend suggesting that representation of older adults increased with year of publication. The primary outcome for the included trials was overall survival, except for one, which used best supportive care as the primary outcome. All 11 studies reported age-stratified data for the primary outcome, (3 in supplemental data). Across 11 trials, we found no statistically significant difference in overall survival between the older and younger age groups, nor any reported age-stratified outcomes for adverse effects. Conclusions: Although no statistically significant difference in primary outcomes was observed between different age groups, it is important to recognize that this finding is potentially confounded by the underrepresentation of older adults in these studies. We must give careful attention to the barriers that older adults with HNSCC face in clinical trial enrollment, and future research should specifically examine age-stratified outcomes, particularly adverse effects and patient-reported outcomes, to better guide management in this insufficiently studied population.