Compared to chemotherapy, immune checkpoint inhibitors (ICIs) demonstrated a lower risk of neurological adverse events (NAEs), according to the results of a meta-analysis that evaluated 39 randomized clinical trials (RCTs) of stage 2/3. The relationship between ICI and NAE justified the analysis.111
The overall risk of ENA was lower in the ICI group than in the control group with a relative risk [RR] 0.59 (95% CI, 0.45-0.77; I2 = 95%, P I2 = 93%; P I2 = 26%; P = 0.25). Investigators identified I values of 25%, 50% and 75% to represent low, moderate and high heterogeneity respectively.
The RR was found to be significantly lower in the ICI group when observing peripheral neuropathy (RR, 0.30; 95% CI, 0.17-0.51; I2 = 91%; P I2 = 83%; P I2 = 74%; P I2 = 68%; P = 0.02) and paresthesia (RR, 0.29; 95% CI, 0.13-0.67; I2 = 58%; P = 0.003) were significantly lower in the ICI group.
The data pool from the 39 trials included 23,705 patients; 16,135 patients (68.0%) were male and 7,866 patients (33.1%) were Caucasian. Eighteen of these clinical trials tested PD-1 inhibitors (14 with pembrolizumab [Keytruda] and 4 with nivolumab [Opdivo]11 PD-L1 inhibitors tested (7 with atezolizumab [Tecentriq]2 with avelumab [Bavencio]and 2 with durvalumab [Imfinzi]), 9 CTLA-4 inhibitors tested (8 with ipilimumab [Yervoy] and 1 with tremelimumab), and 1 trial was a study of dual checkpoint inhibitors. In the 39 trials that met the inclusion criteria, the analysis counted 10,595 patients in the ICI arm and 13,110 patients in the control arm, defined as trials using treatment regimens including chemotherapy, targeted therapy, vaccines or combination therapies.
NAEs of all grades were significantly lower with ICI compared to the control arm (15.0% versus 19.9%, respectively). Peripheral neuropathy, which was reported in 23 trials, was significantly lower in patients in the ICI group compared to those in the control group (4.2% versus 10.5%, respectively). Headache was more common in the ICI group than in the control group (11.6% versus 8.8%, respectively; RR, 1.32; 95% CI, 1.10-1.59; I2 = 51%; P = 0.008). Dysgeusia was less common in patients in the ICI group than in patients in the control group (4.9% versus 14.4%, respectively).
Investigators found NAEs in 317 patients (6.0%) in the ICI arm and in 757 patients (17.4%) in the chemotherapy arm. The overall risk of ENA was significantly lower in the ICI group compared to the chemotherapy arm. Twelve trials reported a significantly lower risk of peripheral neuropathy in the ICI arm compared to the chemotherapy arm (1.4% versus 10.8%, respectively). Ten trials reported a significantly lower risk of dysgeusia in the ICI arm compared to the chemotherapy arm (1.9% versus 6.5%, respectively). Five trials reported a significantly lower risk of paresthesia in the ICI arm compared to the chemotherapy arm (1.3% versus 4.4%, respectively).
NDEs were reported in 389 patients (17.5%) in the ICI arm and in 223 patients (12.4%) in the placebo arm. Three trials reported a significantly higher risk of headache with ICI (RR, 1.63; 95% CI, 1.32-2.02; I2 = 4%; P = .35).
Investigators observed a lower overall risk of ENA in patients who received ICI treatment than in control groups. Peripheral neuropathy, headache and dysgeusia were also less common with ICI than with chemotherapy. However, it should be noted that patients who received placebo saw less risk of ENA than patients who received ICI. Further research is needed to better understand the association of NAEs with ICI use.
Farooq MZ, Aqeel SB, Lingamaneni P, et al. Association of immune checkpoint inhibitors with neurological adverse events: a systematic review and meta-analysis. JAMA Netw Open. 2022;5(4):e227722.. doi:10.1001/jamanetworkopen.2022.7722