Neoadjuvant versus Adjuvant Chemoimmunotherapy for Stage II-IIIB Non-Small Cell Lung Cancer

BACKGROUND:In patients with resectable non-small cell lung cancer (NSCLC), recent trials demonstrate survival benefit of chemoimmunotherapy over chemotherapy alone in both the neoadjuvant and adjuvant settings. To date, there is no direct comparison between neoadjuvant and adjuvant protocols. We compared neoadjuvant versus adjuvant chemoimmunotherapy for resectable Stage II-IIIB NSCLC. METHODS:We queried the National Cancer Database for patients who had undergone surgery for Stage II-IIIB NSCLC who had received either neoadjuvant or adjuvant chemoimmunotherapy between 2015-2020. We used inverse probability weighting to adjust for confounding variables and employed Kaplan-Meier survival curves and Cox regression (hazard ratio [95% confidence interval]) to explore the relationship between treatment groups and overall survival (OS) at 3-years postoperatively. RESULTS:The inverse probability weighted cohort represented 2,119 weighted patient cases (neoadjuvant = 1,034; adjuvant = 1,085). Kaplan-Meier analysis demonstrated a significant OS benefit for neoadjuvant chemoimmunotherapy compared to adjuvant chemoimmunotherapy in the weighted cohort (3-year OS: 77% [71-83%] vs. 68% [64-72%]; p=0.035). On adjusted Cox regression, neoadjuvant chemoimmunotherapy was associated with a significant OS benefit (0.70 [0.50-0.96]; p=0.027). Amongst patients for whom pathologic stage data was available, 25% of patients receiving neoadjuvant chemoimmunotherapy had a pathologic complete response, with an additional 32.5% being downstaged. CONCLUSIONS:Neoadjuvant chemoimmunotherapy confers a significant OS benefit over adjuvant chemoimmunotherapy for patients with resectable Stage II-IIIB NSCLC. While randomized trials are needed to confirm our findings, strong consideration should be given to administering neoadjuvant chemoimmunotherapy to patients who are predetermined to receive systemic treatment.