Switching from canonical interval dosing to extended interval dosing of immune checkpoint inhibitors (ICIs) does not increase the incidence of immune-related adverse events (irAEs), according to study results published in the Journal of the National Cancer Institute.
In this retrospective study, researchers analyzed patients with solid tumors who were treated with at least 1 cycle of extended interval dosing ICI monotherapy after switching from canonical interval dosing, or they were treated with upfront extended interval dosing.
The final analysis included 812 patients who had melanoma (n=456), non-small cell lung cancer (NSCLC; n=204), renal cancer (n=141), and other cancers (n=11).
Extended interval dosing consisted of pembrolizumab at 400 mg every 6 weeks or nivolumab at 480 mg every 4 weeks. Canonical interval dosing consisted of pembrolizumab at 200 mg every 3 weeks or nivolumab at 240 mg every 2 weeks.
Overall, 66.5% of patients received nivolumab, and 33.5% received pembrolizumab. About one-third of patients (32.3%) started upfront with extended interval dosing, and 67.7% started with canonical before switching to extended interval dosing. The main reason for the switch from canonical to extended interval dosing was physician’s choice (84.6%), but some patients (13.2%) requested the switch.
Outcomes by Dosing Interval and Cancer Type
During upfront canonical interval dosing, 40.9% of patients had irAEs of any grade, and 3.1% had grade 3-4 irAEs. After switching to extended interval dosing, 37.1% of patients had irAEs of any grade, and 4.8% had grade 3-4 irAEs.
The researchers pointed out that 44.6% of any-grade irAEs and 52.2% of grade 3-4 irAEs that occurred during extended interval dosing occurred in patients who had not experienced any irAEs during canonical interval dosing. A minority of patients (6.2%) switched back from extended to canonical interval dosing, mainly due to toxicity (44.1%).
However, in a multivariable analysis, extended interval dosing was associated with a lower probability of irAEs of any grade (adjusted odds ratio [aOR], 0.83; 95% CI, 0.64-0.99; P =.047). There was no significant difference in the likelihood of grade 3-4 irAEs between extended and canonical interval dosing (aOR, 1.55; 95% CI, 0.81-2.94; P =.18).
Melanoma patients had a lower risk of any grade irAEs after switching to extended interval dosing (aOR, 0.59; 95% CI, 0.41-0.85; P =.005) and a similar risk of grade 3-4 irAEs (aOR, 1.06; 95% CI, 0.43-2.60; P =.89).
There was no significant difference between canonical and extended interval dosing in NSCLC patients for any-grade irAEs (aOR, 1.31; 95% CI, 0.80-2.12; P =.27) or grade 3-4 irAEs (aOR, 2.97; 95% CI, 0.73-11.98; P =.12).
Common irAEs during canonical interval dosing were dermatitis (14%), thyroiditis (12.6%), and asthenia (10.4%). The spectrum of irAEs did not change after switching to extended interval dosing, the researchers noted.
In patients treated upfront with extended interval dosing, 40.8% had any-grade irAEs, and 5.3% had grade 3-4 irAEs. A minority of patients (6.8%) switched to canonical interval dosing, mainly due to toxicity (38.8%).
Patients who had irAEs during extended interval dosing had longer overall survival (OS) than patients who reported no irAEs.
Among patients who switched to extended interval dosing, the median OS was not reached for those who had irAEs and was 40.4 months for those who did not (P =.005).
Among patients who received upfront extended interval dosing, the median OS was 34.2 months for those who had irAEs and 23.4 months for those who did not (P =.01).
These results suggest that irAEs might be a “surrogate of clinical activity” in the setting of extended interval dosing, the researchers noted. They added that switching ICI treatment from canonical to extended interval dosing appears to be a safe option.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Cantini L, Paoloni F, Pecci F, et al. Safety of extended interval dosing immune checkpoint inhibitors: A multicentre cohort study. J Natl Cancer Inst. Published online April 12, 2023. doi:10.1093/jnci/djad061