In a systematic review and meta-analysis reported in The Lancet Oncology, Fujiwara et al found that the addition of immune checkpoint inhibitors to perioperative therapy in patients with solid tumors was associated with an increased risk of grade 3 and 4 treatment-related adverse events and adverse events leading to treatment discontinuation.
Study Details
The study included identification of randomized trials evaluating the addition of immune checkpoint inhibitors to neoadjuvant or adjuvant therapy for solid cancer reported through August 2023. A total of 28 trials with just under 17,000 patients were included in the analysis.
Key Findings
Overall, the addition of immune checkpoint inhibitor therapy was associated with a nonsignificant increased risk of treatment-related death (odds ratio [OR] = 1.76, 95% confidence interval [CI] = 0.95–3.25, P = .073), with the finding being consistent across immune checkpoint inhibitor subtypes. A total of 40 fatal toxicities occurred among the 9,864 patients treated with immune checkpoint inhibitors, with pneumonitis being the most common (n = 6); 13 fatal toxicities occurred among 7,112 patients not treated with immune checkpoint inhibitors.
Overall, the addition of immune checkpoint inhibitor therapy significantly increased the risk of treatment-related adverse events of any grade (OR = 2.60, 95% CI = 1.88–3.61, P < .0001), grade 3 and 4 treatment-related adverse events (OR = 2.73, 95% CI = 1.98–3.76, P < .0001), serious adverse events (OR = 1.96, 95% CI = 1.58–2.44, P < .0001), and adverse events leading to treatment discontinuation (OR = 3.67, 95% CI = 2.45–5.51, P < .0001).
Analysis of immune checkpoint inhibitors vs placebo, a design primarily used in adjuvant therapy trials, showed that immune checkpoint inhibitor treatment was associated with an increased risk of treatment-related death (OR = 4.02, 95% CI =1.04–15.63, P = .044) and treatment-related grade 3 and 4 adverse events (OR = 5.31, 95% CI = 3.08–9.15, P < .0001). The addition of immune checkpoint inhibitor treatment in the neoadjuvant setting was not associated with an increased risk of treatment-related death (OR = 1.11, 95% CI = 0.38–3.29, P = .84) or treatment-related grade 3 and 4 adverse events (OR = 1.17, 95% CI = 0.90–1.51, P = .23).
The investigators concluded, “The addition of immune checkpoint blockade to perioperative therapy was associated with an increase in grade 3–4 treatment-related adverse events and adverse events leading to treatment discontinuation. These findings provide safety insights for further clinical trials assessing neoadjuvant or adjuvant immune checkpoint blockade therapy. Clinicians should closely monitor patients for treatment-related adverse events to prevent treatment discontinuations and morbidity from these therapies in earlier-stage settings.”
Abdul Rafeh Naqash, MD, of the Stephenson Cancer Center, University of Oklahoma, Oklahoma City, is the corresponding author for The Lancet Oncology article.
Disclosure: The investigators reported that there was no external funding for the study. For full disclosures of the study authors, visit thelancet.com.
