Real-world outcomes and patterns of recurrence in a cohort treated with PACIFIC protocol: A single-center retrospective study.

Abstract

e20089 Background: Lung cancer is the leading cause of cancer-related mortality. The PACIFIC trial established that one year of adjuvant durvalumab after concurrent chemoradiation therapy (cCRT) significantly improves progression-free survival (PFS) and overall survival (OS) in stage III non-small cell lung cancer (NSCLC). We evaluated the real-world efficacy and tolerability of this regimen and identified variables that may improve outcomes. Methods: We retrospectively analyzed 57 patients with unresectable stage III NSCLC treated with cCRT followed by durvalumab at Mount Sinai Comprehensive Cancer Center (2018–2022). PFS, OS were evaluated using Kaplan-Meier and log-rank tests. Predictors of PFS and OS were analyzed via Multivariate Cox regression analysis. Associations between variables were assessed using chi-squared, Fisher’s exact, and Mann-Whitney U tests. Analyses were performed in R (v4.4.2) using the “survival,” “survminer,” “dplyr,” “tidyr,” “ggplot2,” “gt,” and “epitools” packages. Results: The cohort was predominantly male (61.4%), white (84.2%), Hispanic (66.7%), stage IIIA/IIIB disease (87.8%) and adenocarcinoma histology (61.4%). All patients received cCRT, with 29.8% receiving post-cCRT chemotherapy for a total of 12 weeks (caCRT). Median PFS was 22 months (95% CI, 15–35), and PFS rates at 12, 24, and 36 months were 64.9%, 42.1%, and 35.1%, respectively. Median OS was not reached, with OS rates 82.4%, 70.1% and 63.1% at same timelines. Multivariate analysis identified >10 durvalumab cycles (PFS: HR 0.85, 95% CI, 0.80–0.91, p < 0.001; OS: HR 0.79, 95% CI, 0.68–0.93, p = 0.004), caCRT (PFS: HR 0.31, 95% CI, 0.12–0.80, p = 0.02; OS: HR 0.24, 95% CI, 0.06–0.98, p = 0.047) and adenocarcinoma (OS: HR 0.244, 95% CI, 0.062-0.964, p= 0.044) as significant baseline predictors. 86.2% of progression were metastatic. Time to local recurrence (TTLR) and time to distant metastasis (TTDM) were 18 and 14.5 months, respectively (p = 0.46). Patients receiving second-line immunotherapy had a longer time to third line (TTTL), 17 vs. 3 months (p < 0.001). Significant side effects (SSEs) occurred in 29 patients (29.8%) at a median of 5 cycles (95% CI, 3–12) mainly pneumonitis, thyroiditis, and dermatitis, leading to therapy discontinuation. Conclusions: Our study highlights the reproducibility of the PACIFIC protocol in a predominantly Hispanic cohort. caCRT may improve systemic control and reduce metastatic progression, the most common recurrence type in our study. Durvalumab was overall well tolerated, however the risk reduction in progression and mortality is seen after at least 10 cycles, a threshold not met by patients with SSEs. Second-line immunotherapy was associated with prolonged TTTL, suggesting potential benefits from immune system reinvigoration, warranting further investigation in larger, multicentric studies.