Pathologic complete response with neoadjuvant chemoimmunotherapy in clinical stage II–III NSCLC: A large real-world analysis including older adults.

8055 Background: Neoadjuvant chemoimmunotherapy is now the standard for clinical stage II-III non-small cell lung cancer (NSCLC) following CheckMate 816. However, older adults and socioeconomic factors have been underrepresented in clinical trials. This study aims to evaluate the impact of age and basic socioeconomic factors on pathological complete response (pCR) after neoadjuvant chemoimmunotherapy. Methods: Data from the National Cancer Database (NCDB) were obtained for patients diagnosed with clinical stage II-III NSCLC between 2019 and 2023 who underwent neoadjuvant chemotherapy (CT; 2019-2021) or chemoimmunotherapy (CTIO; 2022-2023) with complete T, N, and M staging data, as well as post-pathologic status (ypT, ypN). Those receiving neoadjuvant radiotherapy and with clinical or pathologic metastatic disease were excluded. Groups were stratified based on age (<75 vs ≥ 75 years). Group comparisons were performed using chi-square testing. The primary outcome was pCR, analyzed using univariate and multivariable Cox regression models. A p-value of <0.05 was considered statistically significant. Results: A total of 993 patients received CT alone, while 2,819 received CTIO. Among patients ≥ 75 years, pCR rates were significantly higher in the CTIO group compared with CT alone (25% vs 5%, p<0.001). This pattern was similar in patients <75 years (29% vs 8%, p<0.001). Among CTIO receivers, pCR rates did not differ significantly by age (25% ≥75 vs 29% <75; p=0.051) (Table 1). Patients with ≥10 lymph nodes examined had lower pCR rates compared with those with fewer nodes examined (26% vs 37%; p<0.001). On multivariate analysis, higher nodal stage (N1–N3; OR 1.23, 1.02-1.49, p=0.035) and non-adenocarcinoma histologies (OR 1.26, 1.07-1.49, p=0.006) were independently associated with higher odds of pCR. Notably, age, sex, race, and rural/urban residence were not independently associated with pCR, and no significant differences in race or rural/urban status were observed between groups. Conclusions: To our knowledge, this is the largest real-world analysis of neoadjuvant chemoimmunotherapy outcomes in older adults with clinical stage II-III non–small cell lung cancer. We found comparable pCR rates across age groups, supporting the use of this approach in older individuals. While racial disparities have been described in access to neoadjuvant therapy, our study suggests similar response rates across racial groups who underwent treatment. Higher nodal status was independently associated with pCR, which may be explained by greater tumor immunogenicity. These findings are hypothesis-generating and warrant validation in further prospective studies. Pathologic complete response rate by age status. Factors pCR(n=811) No pCR (n=2008) P value (Chi-square) Age ≥ 75< 75 115 (25%)696 (29%) 345 (75%)1663 (71%) 0.051 pCR=Pathologic Complete Response.