Optimizing Treatment for Human Papillomavirus-Associated Oropharyngeal Cancer in Older Adults

SUMMARY Human papillomavirus-associated oropharyngeal cancer (OPC) is one of the fastest rising causes of cancer incidence (3%/year) in the US, with a pronounced increase (≥4%/year) among older adults (≥65 years). The OPC burden is projected to double (>30,000 new cases annually) over the next few decades, with >60% of new cases occurring in patients aged ≥65 years. Although standard of care treatment for OPC results in excellent survival, it can cause devastating chronic toxicity and impaired long-term quality of life (QOL). As a result, a number of clinical trials and real-world studies have evaluated protocols to de-intensify treatment for patients with OPC. However, none of the studies considered the evolving OPC epidemiology and assessed the effect of aging and multimorbidity on treatment toxicity, oncologic outcomes, and QOL. Due to their comorbidity burden and narrow therapeutic index, older adults with OPC are more susceptible to treatment-related adverse events (AEs), suffer from worse QOL, and have an increased mortality risk from competing events. In addition, patient preferences regarding the tradeoff between survival and treatment toxicity, data that are critical to guide preference-concordant shared decision-making, have not been fully characterized in this population. As a result, treatment of OPC among older adults is guided by inappropriate extrapolation of data from studies in younger patients. To address this critical gap, disease simulation modeling can be used to generate in-silico trials to compare harms vs benefits of different treatment paradigms over the patient’s lifetime in the context of aging and multimorbidity. This project will leverage several large representative data sources with over 200,000 OPC (>122,000 older adult) cases to characterize treatment outcomes among patients with OPC as a function of age and multimorbidity and evaluate preferences for the tradeoff between survival and treatment toxicity among 150 OPC survivors. We will use these collective inputs to synthesize a novel micro-simulation model (Simulation model of OropharyngeaL cAnCEr treatment among older adults [SOLACE]), and then perform in- silico trials using SOLACE to compare harms and benefits of OPC treatment, particularly among older adults and those with multimorbidity. Our Aims are: (1) To characterize the impact of aging and multimorbidity on (a) treatment outcomes (AEs, oncologic outcomes, QOL) and (b) treatment priorities and preferences among patients with OPC; (2) To synthesize, calibrate, and validate a micro-simulation model (SOLACE) of OPC treatment outcomes over the survivorship duration in association with age and multimorbidity; and (3) To compare the harms vs benefits of common treatment paradigms (including de-intensification) over the lifetime of patients with OPC in the context of aging and multimorbidity using SOLACE. Study findings could transform clinical decision-making for OPC, maximize benefits and reduce harms, and inform evidence-based, patient- centered, and preference-concordant decision-making for this rapidly growing patient population.