Real world analysis comparing chemoradiation with durvalumab vs chemoradiation alone in locally advanced, unresectable, stage III non-small cell lung cancer.

e20084 Background: In the randomized phase III PACIFIC trial, combining durvalumab with chemoradiation (CRT) resulted in an improvement in overall-survival (OS) and progression free survival (PFS) when compared to CRT alone, regardless of PD-L1 status in locally advanced, unresectable stage III non-small cell lung cancer (NSCLC). There are limited real-world studies examining long term outcomes of locally advanced, unresectable stage III NSCLC. Methods: We conducted a retrospective analysis including adult patients with stage IIIB/C NSCLC at Cleveland Clinic Foundation from 1/2010-12/2022. Baseline variables included age, sex, race, performance status, and smoking history. RECIST 1.1 response criteria was used to assess treatment response. Multivariable cox regression was used to find associations with overall survival (OS) and progression free survival (PFS). Results: We identified 290 patients with Stage IIIB/C NSCLC, 140 patients were non-squamous cell carcinoma (non-SCC) and 150 patients with squamous cell carcinoma (SCC). Median age was 66 years, among which 61% were male, 83% white, and around 52% were current smokers. 72% received only CRT and 28% received CRT followed by Durvalumab. In the CRT alone group, the most common regimens used were Carboplatin and Paclitaxel (n=128, 44%) and Cisplatin and Etoposide (n=32, 11%). In the CRT + Durvalumab group, the most common regimen was Carboplatin and Paclitaxel (n=78, 27%). The most common radiation dose was 60 Gy delivered in 30 fractions (71%, 74%). The 2-year and 5-year OS for Non-SCC was 47% and 35% respectively. The 2-year and 5-year overall OS for SCC was 47% and 25% respectively. The median OS with CRT + Durvalumab was 37 months (95%CI: 26-NR) vs. 18 months (95%CI: 15-21) for CRT alone. In multivariable cox regression, CRT + Durvalumab was associated with improved OS (HR 0.5, 95%CI 0.40-0.79, p<0.001) compared to CRT alone. Increasing age (HR 1.02, 95%CI 1.01-1.04, p= 0.006) and male gender (HR 1.41, 95%CI 1.05-1.89, p= 0.020) were associated with worse PFS. Similarly, CRT + Durvalumab were associated with improved PFS (0.64, 95%CI 0.47-0.89, p= 0.005). Though CRT + Durvalumab was associated with a significant improvement in OS for Non-SCC (HR 0.50, 95%CI 0.31-0.81, p= 0.003), it was not statistically significant for SCC (HR 0.74, 95%CI 0.48-1.15, p = 0.2). Conclusions: We found that addition of Durvalumab to CRT was associated with increased OS and PFS in locally advanced, unresectable stage III NSCLC, like the results to the PACIFIC trial. This retrospective analysis did not show significant benefit in OS for SCC patients, which is different compared to the trial, and this could be due to study power, and overall fitness and health of the patients. Our study showed that SCC are associated with lower long-term survival compared to non-SCC subtypes.