Treatment-related Death in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and...

Area of Science:

• Oncology
• Immunotherapy
• Clinical Trials

Background:

• Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment.
• Understanding the safety profile, specifically treatment-related death (TRD), is crucial for clinical decision-making.
• Differential risks associated with various ICI classes require detailed investigation.

Purpose of the Study:

• To conduct a meta-analysis assessing the risk of treatment-related death (TRD) in cancer patients treated with immune checkpoint inhibitors (ICIs).
• To compare the TRD associated with CTLA-4 inhibitors versus PD-1/PD-L1 inhibitors.
• To evaluate the impact of cancer type on TRD risk with ICIs.

Main Methods:

• A systematic meta-analysis was performed using data from Medline and Google Scholar.
• Included were randomized phase II and III trials of cancer patients treated with ipilimumab, pembrolizumab, nivolumab, tremelimumab, and atezolizumab.
• Data extraction focused on patient characteristics, treatment regimens, and treatment-related deaths.

Main Results:

• Eighteen clinical trials were included in the final analysis.
• Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (ipilimumab, tremelimumab) were associated with a significantly higher odds ratio for TRD (1.80; 95% CI 1.25-2.59; P=0.002).
• Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors (nivolumab, pembrolizumab, atezolizumab) showed no increased risk of TRD (OR 0.63; 95% CI 0.31-1.30; P=0.22).
• The type of cancer treated did not appear to influence the risk of TRD.

Conclusions:

• High-dose CTLA-4 inhibitors (10 mg/kg) are associated with an increased risk of treatment-related death compared to control regimens.
• PD-1/PD-L1 inhibitors do not appear to carry the same increased risk of treatment-related death.
• Clinicians must be aware of these differential risks to appropriately counsel patients regarding ICI therapy.