FP10.01 Survival in Advanced SCLC: Projected Impact of Immuno-Oncology-Associated Durable Response on Population Health Gains in US

Abstract

Historically, prognosis for patients with metastatic small cell lung cancer (SCLC) treated with chemotherapeutic agents has been poor. Immuno-oncology (I-O) therapies, such as nivolumab and ipilimumab, have been associated with improved response and durable survival in SCLC. Healthcare decision-makers considering reimbursement are required to balance expected treatment costs with predicted lifetime costs and health outcomes. These predictions are sensitive to the proportion of I-O treated patients achieving a durable response; however, this information is typically unavailable at the time of decision-making. Consequently, the objective of this study was to quantify historical age-specific US SCLC survival rates and compare these with expected I-O survival for a range of clinically plausible durable response rates. Overall survival (OS) for patients with metastatic SCLC between 2010-2015 were derived from the Surveillance, Epidemiology, and End Results (SEER) database stratified by age at diagnosis (40-90 years). OS for patients receiving I-O therapy was based on those with recurrent SCLC from the nivolumab arm of the Checkmate-032 study. Mean OS was estimated using a delayed mixture model, applying a piecewise exponential and assuming a fraction of patients surviving at the end of the 26 month follow-up period (∼21% patients) achieved a durable response. A plausible base case fraction was derived using long term follow-up of patients treated with nivolumab in NSCLC, indicating a 10% durable response fraction. For those achieving a durable response background general population mortality was applied. Incremental survival was estimated by comparing historical outcomes (SEER) to long-term survival estimates for patients receiving I-O therapy. Estimates of incremental survival benefit were extrapolated to the US population using age-adjusted incidence data for patients with advanced (stage III/IV) disease. Age-adjusted incidence data was applied to all incident patients to assess the potential population health gains associated with I-O therapy. Historic diagnosis with advanced SCLC (SEER) was associated with an expected survival of 8.4 months (baseline age: 70 years). By contrast, mean OS in I-O treated patients was estimated to be 29.5 months, equivalent to incremental survival gains of 21.2 months. At ages 40 and 90 real-world benchmark expected survival was 12.3 months and 4.0 months respectively, I-O-treated mean OS ranged between 62.2 months (49.9 month gain at age 40) and 13.3 months (9.3 month gain at age 90) for the 10% of patients surviving and achieving a durable response after 26 months of follow up. Applying age-adjusted incremental survival estimates to the incident SCLC population (13,570 patients) was associated with a potential gain of 27 thousand life years, with more pronounced gains in life expectancy in younger compared with older cohorts. Patients with recurrent SCLC have historically experienced few treatment options and poor outcomes. Potential health gains associated with I-O therapies are significant at both the patient and population level but should account for age to avoid bias and improve accuracy. This study quantifies expected OS gains associated with I-O therapy using a remission rate based on trial data designed to assist decision-makers’ expertise when considering the robustness of predicted survival estimates.