Chemoradiotherapy Combined with Immunotherapy in Stage III Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Efficacy and Safety Outcomes.

Background: Since the success of the PACIFIC trial, durvalumab has become the clear standard of care for many patients with stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CRT). However, the duration of immune consolidation and the efficacy and safety of different immune agents remain unclear. We conducted a systematic review of relevant studies.

Methods: We searched all the relevant studies in PubMed, Embase, and Cochrane Library databases. We also reviewed abstracts of relevant conferences to prevent omissions. The meta-analysis was performed using Stata version 16.0.

Results: CRT combined with immunotherapy can improve progression-free survival (PFS) (hazard rate [HR]: 0.60, 95% confidence interval [CI, 0.55-0.60) and overall survival (OS) (HR: 0.59, 95% CI, 0.53-0.66) compared with no immunotherapy. The pooled 24-month PFS and 24-month OS rates were 48.1% (95% CI, 43.5-52.7%) and 71.3% (95% CI, 67.3-75.2%), respectively. Subgroup analysis showed that 24-month OS rates were 60.7% (95% CI, 51.0-70.3%) and 77.4% (95% CI, 73.2-81.7%) at 1 year and 2 years of immune consolidation, respectively. The pooled 1-year completion rate for immune consolidation was 35.6% (95% CI, 31.3-39.8%). The pooled rate of pneumonitis for all grades was 41.7% (95% CI, 31.9-51.9%). The pooled rate of pneumonitis ≥ grade 3 was 6.7% (95% CI, 5.0-8.5%). The incidence of pneumonitis ≥ grade 3 after 1 year of immunotherapy is 4.8% (95% CI, 3.1-6.5%). The incidence of pneumonitis ≥ grade 3 after 2 years of immunotherapy is 5.1% (95% CI, 2.9-7.3%).

Conclusions: Prolonging the duration of immunotherapy consolidation increases survival benefits in patients with stage III NSCLC without causing higher side effects. Older patients, due to high incidence of pneumonia and low immunotherapy completion rate, have less survival benefit.