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.

Background/Objectives: Immuno-oncology plus tyrosine kinase inhibitor (IO+TKI) combination therapy is an essential first-line therapy for advanced renal cell carcinoma (RCC). However, reports of its efficacy and safety as late-line therapy are lacking. This study aimed to examine the efficacy and safety of IO+TKI combination therapy as a late-line therapy for patients with RCC. Methods: We retrospectively examined 17 patients with RCC who received IO+TKI combination therapy as a second-line therapy or beyond (pembrolizumab plus axitinib, n = 10; avelumab plus axitinib, n = 5; nivolumab plus cabozantinib, n = 2). Results: The overall response and disease control rates of IO+TKI combination therapy were 29.4% and 64.7%, respectively. The median overall survival was not attained. Progression-free survival was 552 days, and 94.1% of patients (n = 16) experienced adverse effects (AEs) of any grade; moreover, 41.2% of patients (n = 7) experienced grade ≥ 3 immuno-related AEs. Conclusions: IO+TKI combination therapy may be a late-line therapy option for RCC.

Background: Pharmacological options for refractory cancer pain are limited. This study aimed to investigate the efficacy and safety of the combined use of low-dose methadone and ongoing opioid treatment for uncontrolled cancer pain. Methods: This was a prospective, open-label study. Participants were patients with uncontrolled cancer pain despite dose titration of opioids. Patients received low-dose methadone (starting dose of 5 or 10 mg/day) combined with another ongoing opioid therapy. The primary outcome was the proportion of responders (defined as ≥33% reduction in average pain intensity on the numerical rating scale [NRS]) on day 15. Pain intensity and adverse events according to the Patient-Reported Outcome Common Terminology Criteria for Adverse Events were evaluated at baseline, on days 8 and 15. Results: Nineteen patients participated in this study, 11 (57.9%) of whom had neuropathic pain. The mean daily oral morphine equivalent dose before combination was 112.6 mg. The primary outcome occurred in 13 (68.4%) of patients (95% CI, 43.4 to 87.4). The mean average NRS was 5.9 at baseline, which decreased significantly to 4.2 and 3.3 on days 8 and 15 (P < .001), respectively. The worst pain intensity on NRS decreased significantly over time. Adverse effects, including nausea, vomiting, constipation, and somnolence, which were new or had worsened from baseline, were reported in 26.3%, 26.3%, 5.3%, and 26.3%, respectively. Delirium was observed in one patient. Conclusion: Low-dose methadone with ongoing opioid treatment shows potential efficacy in the management of uncontrolled pain with acceptable adverse events. ClinicalTrials.gov identifier: UMIN000038924

Background: While opioid analgesics are widely used to manage moderate-to-severe cancer-related pain, dosing is mostly based on subjective pain reports rather than objective physiological indicators, potentially contributing to inconsistent dosing and suboptimal pain control. This study investigated whether model-predicted oxycodone serum concentrations could guide opioid dosing and whether wearable-derived heart rate and step count, combined with these predictions, could complement conventional numerical rating scale (NRS) pain assessments. Methods: Sixteen patients with advanced genitourinary cancer receiving oxycodone were prospectively monitored. Clinically collected serum concentrations were used to simulate individual pharmacokinetic profiles. Pain intensity was assessed using the NRS, and physiological parameters were recorded using wearable devices. Linear mixed-effects models were constructed to evaluate the associations between simulated serum oxycodone concentrations, NRS, and physiological variables. Results: In the linear mixed-effects model, simulated serum oxycodone concentrations were significantly associated with lower NRS scores (β = −0.26, P = .0177). Although neither heart rate nor step count independently predicted NRS, incorporating heart rate into the model improved the overall fit. Thus, heart rate may capture pain-related physiological responses not fully explained by oxycodone concentration alone, thereby enhancing the explanatory power of the model. Conclusions: Model-based simulated serum oxycodone concentrations may serve as an objective reference for individualized pain assessment and opioid titration. Combining wearable-derived physiological signals, particularly heart rate, with model-predicted oxycodone concentrations may further improve the precision and adaptability of pain management in palliative care.