Real-world data on efficacy/safety and economic impact of nivolumab administered every 2 and 4 weeks among Japanese patients.

AIM: A new treatment interval for nivolumab administration at 480 mg every 4 weeks, in addition to 240 mg every 2 weeks, was approved in Japan in 2020. Using model-based evaluation, it was speculated that the effects or safety of nivolumab do not differ between the two treatment intervals; however, real-world data on nivolumab efficacy, safety, and economic impact are lacking. Accordingly, we aimed to examine the effects of nivolumab treatment intervals (2 weeks vs. 4 weeks) in terms of efficacy, safety, and economic impact in Japanese patients with cancer. METHODS: We retrospectively analyzed 126 patients treated with nivolumab. The patients were divided into two groups depending on whether they received nivolumab at 240 mg every 2 weeks (2-week group) or 480 mg every 4 weeks (4-week group). RESULTS: Efficacy results found no significant difference between the 4- and 2-week groups considering median overall survival (p = 0.70) and median progression-free survival (p = 0.57). The incidence of any grade and ≥  grade 3 immune-related adverse events did not differ between the 4-week and 2-week groups (any grade, p = 0.13; ≥  grade 3, p = 0.36). Excluding drug costs, the 4-week group had significantly lower medical costs than the 2-week group (2-week vs. 4-week: mean, 94,659 JPY [679.0 USD] vs. 58,737 JPY [421.3 USD]; p < 0.05). CONCLUSION: Collectively, our findings suggest that nivolumab 480 mg every 4 weeks may be more effective than nivolumab 240 mg every 2 weeks in terms of economic impact.

Eosinophil may be a predictor of immune-related adverse events induced by different immune checkpoint inhibitor types: A retrospective multidisciplinary study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause severe immune-related adverse events (irAEs). However, biomarkers for irAEs common to different types of ICIs and cancers have not been reported. This study examined whether eosinophils can be used as a predictor of irAEs. METHODS: Six hundred fourteen patients with cancer (esophageal, gastric, head and neck, lung, melanoma, renal cell, urothelial, and other cancer) received anti-PD-1, anti-PD-L1, or anti-CTLA-4 plus anti-PD-1 therapy. The patients were divided into two groups depending on whether they experienced irAEs (irAE group) or not (non-irAE group). Eosinophils were examined before the two-course treatment. RESULTS: Patients in the irAE group who received anti-PD-1 or anti-CTLA-4 plus anti-PD-1 therapy had higher eosinophils before the two-course treatment than those in the non-irAE group (p < 0.05). The eosinophils in the anti-PD-L1 therapy group tended to increase in the irAE group. Furthermore, eosinophils in gastric, head and neck, lung, melanoma, renal, and urothelial cancers were significantly higher in the irAE group than in the non-irAE group (p < 0.05). The optimal cutoff value for eosinophils against irAEs was 3.0% (area under the curve = 0.668). In multivariate analyses, eosinophils of ≥3.0% were an independent factor for irAEs (odds ratio: 2.57, 95% CI: 1.79-3.67). CONCLUSION: An increased eosinophil before the two-course treatment may be a predictor of irAEs in various cancers treated with different ICIs.

Development and Evaluation of a Novel Software Program, SAKURA-TDM, for Area Under the Concentration-Time Curve-Guided Vancomycin Dosing: A Short Communication.

BACKGROUND: The area under the concentration-time curve (AUC)-guided dosing of vancomycin has been introduced in Japan; however, the optimal dosing method remains controversial. Here, a novel software program was developed for AUC-guided vancomycin dosing and to estimate the theoretical threshold of the steady-state AUC 24 that could reduce the risk of renal injury. METHODS: A single-center, retrospective, observational study was conducted to develop a novel software program (SAKURA-TDM ver.1.0) for AUC-guided dosing. The estimation accuracy of pharmacokinetic parameters determined using SAKURA-TDM was compared with that of clinically available software programs and assessed with Bland-Altman analysis. In addition, theoretical cutoff points of the steady-state AUC 24 and the predicted trough values were estimated using Youden J statistic approach. RESULTS: The estimation accuracy of pharmacokinetic parameters and AUC determined using SAKURA-TDM was comparable to that of other TDM software programs. Of note, despite a good relationship between the predicted AUC 24 and trough values, the correlation between the predicted AUC 24 and measured trough values was not strong. The cutoff values of the steady-state AUC 24 and the predicted trough value for reducing the probability of a measured trough value of >20 mcg/mL were 513.1 mg·h/L and 15.6 mcg/mL, respectively. CONCLUSIONS: We demonstrated the equivalence of the estimated PK parameters between SAKURA-TDM and other TDM software programs available in Japan. Considering the threshold of both trough values and the steady-state AUC and monitoring of the AUC in a non-steady state, it would be possible to reduce the risk of vancomycin-associated renal injury.