Lower NAE Risk Found in ICI Treatment Vs Chemotherapy

Compared with chemotherapy, immune checkpoint inhibitors (ICIs) demonstrated a lower risk of neurologic adverse events (NAEs), according to findings of a meta-analysis that evaluated 39 phase 2/3 randomized clinical trials (RCTs). The relationship between ICIs and NAEs warranted the analysis.¹¹¹

The overall risk of an NAE was lower in the ICI group than in the control group with a risk ratio [RR] of 0.59 (95% CI, 0.45-0.77; I2 = 95%, P < .001) and was lower in the subgroup of RCTs comparing ICI use with chemotherapy (RR, 0.22; 95% CI, 0.13-0.39; I2 = 93%; P < .001). In the subgroup of RCTs comparing ICI with placebo usage, the overall risk of NAE was significantly higher in the ICI group (RR, 1.57; 95% CI, 1.30-1.89; I2 = 26%; P = .25). Investigators identified I values of 25%, 50%, and 75% to represent low, moderate, and high heterogeneity, respectively.

RR revealed to be significantly lower in the ICI group when observing peripheral neuropathy (RR, 0.30; 95% CI, 0.17-0.51; I2 = 91%; P < .001) and dysgeusia (RR, 0.41; 95% CI, 0.27-0.63 I2 = 83%; P < .001).). In the subgroup analysis of RCTs comparing ICI use with chemotherapy, peripheral neuropathy (RR, 0.09; 95% CI, 0.05-0.17; I2 = 74%; P < .001), dysgeusia (RR, 0.42; 95% CI, 0.21-0.85; I2 = 68%; P = .02), and paresthesia (RR, 0.29; 95% CI, 0.13-0.67; I2 = 58%; P = .003) were significantly lower in the ICI group.

The pool of data from the 39 trials consisted of 23,705 patients; 16,135 patients (68.0%) were men, and 7866 patients (33.1%) were White. Eighteen of these clinical trials tested PD-1 inhibitors (14 with pembrolizumab [Keytruda] and 4 with nivolumab [Opdivo], 11 tested PD-L1 inhibitors (7 with atezolizumab [Tecentriq], 2 with avelumab [Bavencio], and 2 with durvalumab [Imfinzi]), 9 tested CTLA-4 inhibitors (8 with ipilimumab [Yervoy] and 1 with tremelimumab), and 1 trial was a dual checkpoint inhibitor study. In the 39 trials that met the inclusion criteria, the analysis tallied 10,595 patients in the ICI arm and 13,110 patients in the control arm, defined as trials using drug regimens including chemotherapy, targeted therapy, vaccines, or combination therapies.

All-grade NAEs were significantly lower with ICIs compared with the control arm (15.0% vs 19.9%, respectively). Peripheral neuropathy, which was reported in 23 trials, was significantly lower in patients in the ICI group compared with those in the control group (4.2% vs 10.5%, respectively). Headache was more common in the ICI group than the control group (11.6% vs 8.8%, respectively; RR, 1.32; 95% CI, 1.10-1.59; I2 = 51%; P = .008). Dysgeusia was less common in patients in the ICI arm compared with patients in the control group (4.9% vs 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 NAE was significantly lower in the ICI group compared with the chemotherapy arm. Twelve trials reported a significantly lower risk of peripheral neuropathy in the ICI arm vs chemotherapy arm (1.4% vs 10.8%, respectively). Ten trials reported a significantly lower risk of dysgeusia in the ICI arm vs chemotherapy arm (1.9% vs 6.5%, respectively). Five trials reported a significantly lower risk of paresthesia in the ICI arm vs chemotherapy arm (1.3% vs 4.4%, respectively).

NAEs 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 lower overall risk of NAEs in patients who received ICIs treatment than in control groups. Peripheral neuropathy, headache, and dysgeusia were also less common with ICIs than chemotherapy. However, it should be noted that patients who received placebo saw less risk of NAEs than patients who received ICIs. Further research is required to further to understand the association of NAEs with the use of ICIs.

_REFERENCE

_{Farooq MZ, Aqeel SB, Lingamaneni P, et al. Association of immune checkpoint inhibitors with neurologic adverse events: a systematic review and meta-analysis. JAMA Netw Open. 2022;5(4):e227722.. doi:10.1001/jamanetworkopen.2022.7722}