Abstract
Objectives Immune checkpoint inhibitors (ICI) combined with radiotherapy (RT) have emerged as a breakthrough therapy in the treatment of various cancers. The combination has a strong rationale, but data on their efficacy and safety are still limited. Hence, we comprehensively searched the database and performed this study to elucidate the clinical manifestations of this combined strategy. Methods We performed a meta-analysis of randomized trials that compared ICI plus RT with placebo plus RT or ICI alone for the treatment of advanced nonsmall-cell lung cancer (NSCLC) and prostate cancer. The outcomes included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and treatment-related adverse events. A fixed-effects or random-effects model was adopted depending on between-study heterogeneity. Results Three trials involving 1584 patients were included. ICI plus RT was significantly associated with improvement of OS (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.70–0.94, P=0.004), PFS (HR = 0.64; 95% CI 0.56–0.72, P < 0.00001), and DCR (relative risk [RR] = 1.38; 95% CI 1.03–1.84, P=0.03). A significant predictor for PFS with the combination of ICI and RT was age, as a significant improvement in PFS (HR = 0.49; 95% CI 0.37–0.64, P < 0.00001) was observed in NSCLC patients aged under 65 years. In safety analyses, patients receiving ICI plus RT had a significantly higher incidence of dyspnea (RR = 2.43; 95% CI 1.16–5.08, P=0.02) and pneumonitis of grade 3 or higher (RR = 2.78; 95% CI 1.32–5.85, P=0.007). Conclusion The combination of ICI and RT was associated with improved OS, PFS, and DCR. Patients under 65 years will be the dominant beneficiaries. However, the incidence of dyspnea and pneumonia of grade 3 or higher also increased, which deserves our vigilance.
Highlights
Over recent decades, immune checkpoint inhibitors (ICI) are considered a major advance in the treatment of various advanced cancers
We performed a systematic review of the literature and reported the outcomes of patients with solid neoplasm treated with ICI and RT
Two reviewers independently completed the search. ey were searched, with no time restrictions, the following databases for relevant English Journal of Oncology language literature: PubMed (MEDLINE), Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), US-clinical trials, and China National Knowledge Infrastructure Database (CNKI). e following keywords were used: “Neoplasms,” “Neoplasia,” “Cancer,” “Immunotherapy,” “Programmed Cell Death 1 Receptor,” “Programmed Cell Death 1 Ligand 1,” “cytotoxic T lymphocyte antigen-4 (CTLA-4) Antigen,” “Durvalumab,” “Pembrolizumab,” “Atezolizumab,” “Nivolumab,” “Tremelimumab,” “Ipilimumab,” “Radiotherapy,” “randomized controlled trial.” e electronic database search will be supplemented by a manual search of the reference lists of included articles
Summary
Immune checkpoint inhibitors (ICI) are considered a major advance in the treatment of various advanced cancers. With the recent success of radiotherapy (RT) combined with immunotherapy in animal models of various types of cancer, there has been renewed interest in the combination of ICI with RT [2,3,4,5,6,7]. It is not clear whether RT can enhance the effects of ICI in human patients, and the safety of combined therapy has not been fully confirmed.
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