2333 - Concurrent Immunotherapy Improves Progression-Free Survival but Increases Toxicity in Unresectable Stage III NSCLC
Presenter(s)
Y. Qin1, Y. Mo2, P. Li2, X. Liang3, B. Tian2, J. Yu4, and D. Chen5; 1Department of Radiation Oncology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, People’s Republic of China, Jinan, Shandong, China, 2Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China, 3Shandong Second Medical University, Weifang, Shandong, China, 4Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences Department of Radiation Oncology, Jinan, Shandong, China, 5Department of Radiation Oncology and Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
Purpose/Objective(s):
The PACIFIC trial supports immunotherapy (IO) consolidation following concurrent chemoradiotherapy, but a significant proportion of patients do not respond to sequential IO, underscoring the need for better treatment strategies. Clinical trials, such as PACIFIC-2, have explored using IO concurrently with radiotherapy (RT). This study aims to compare the efficacy and safety of concurrent versus sequential IO combined with RT. The hypothesis is that administering IO concurrently with RT may improve progression-free survival (PFS) compared to sequential IO after RT.Materials/Methods:
This study divided patients into two groups based on treatment strategies: IO following RT and IO concurrent with RT, where the latter group is defined as receiving = 1 cycle of chemotherapy and IO during RT. A systematic search of multiple databases identified studies comparing these regimens in unresectable stage III non-small cell lung cancer (NSCLC). Inclusion criteria were: (1) Prospective/retrospective studies on pathologically confirmed unresectable stage III NSCLC; (2) Treatment with IO following or concurrent with RT; (3) Reporting at least one outcome: OS, PFS, or AEs (graded per Common Terminology Criteria for Adverse Events, version 5.0). Exclusion criteria included: (1) Fewer than 10 patients per treatment arm; (2) Sequential chemoradiotherapy; (3) No chemotherapy or IO. Data on OS, PFS, and AEs were analyzed using the "meta" package in R (version 4.1.1). Heterogeneity was assessed by the chi-squared test (P < 0.1) or I² > 50%, with a random-effects model applied if significant. Additionally, valdation data from 185 stage III NSCLC patients from a single-centre corhort study were analyzed for PFS and OS using Kaplan-Meier curves and Cox regression.Results:
The meta-analysis showed improved PFS in the IO concurrent with RT group, with significant differences at 1 year (69.5% vs 57.6%) and 1.5 years (56.3% vs 45.7%). However, OS was slightly better in the IO following RT group, which also had fewer severe AEs (= grade 3: 37.2% vs 52.6%, a 15.4% higher incidence in the concurrent group). Notably, in the arm with the highest incidence of = grade 3 AEs, patients generally had a poorer performance status. A single-center cohort confirmed superior PFS for the concurrent group (HR = 2.039, 95% CI: 1.014–4.322, P = 0.046), after adjusting for factors (age, gender and radiation dose, etc.). While PFS was better in the concurrent group, OS did not improve, possibly due to AEs or insufficient follow-up.Conclusion:
Concurrent IO improves PFS in unresectable stage III NSCLC but also increases toxicity. This study underscores the importance of implementing a stratified treatment strategy based on patients' performance status to determine the optimal approach—whether concurrent or sequential IO. Exploring the treatment time window may be a key factor in optimizing treatment strategies. Furthermore, randomized controlled trials are needed to assess the long-term survival and toxicity of concurrent IO.