Introduction: Outpatient cancer treatment can reduce burden on healthcare providers and improve patients' quality of life. In Japan, the Ministry of Health, Labour and Welfare (MHLW) increased the reimbursement incentive for outpatient antineoplastic prescribing from 6,000 JPY (37.4 USD) to 7,000 JPY (43.7 USD) in 2022.

Aims: This study analyzed nationwide trends in outpatient antineoplastic prescribing surrounding the 2022 reimbursement incentive increase in Japan.

Methods: A serial cross-sectional study was conducted using NDB Open Data, an aggregated national reimbursement claims database published by MHLW. The study period covered fiscal year (FY) 2019 to FY2023 (Apr 2019–Mar 2024). The outcome was defined as the annual outpatient prescribed units of antineoplastic agents per 100,000 population. Prefecture-level paired t-tests (n=47) comparing FY2019 and FY2023 values were performed for four categories: all oral agents, all injectable agents, and their subsets of new oral and new injectable antineoplastic agents. New antineoplastic agents were defined by MHLW as the 429 category including immunotherapeutic and molecular-targeted agents. p < 0.05 was considered statistically significant.

Results: For all oral antineoplastic agents, the mean (95%CI) outpatient prescribed units per 100,000 population increased from 324,815 (315,288–334,341) in FY2019 to 393,442 (382,599–404,285) in FY2023; for new oral agents, from 231,395 (224,939–237,852) to 298,940 (291,144–306,736). The mean difference was 68,627 (65,767–71,487; p<0.001) for all oral agents and 67,544 (64,905–70,184; p<0.001) for new oral agents.
For all injectable antineoplastic agents, the mean increased from 10,099 (9,619–10,579) to 12,475 (11,918–13,033); for new injectable agents, from 4,562 (4,366–4,757) to 6,324 (6,059–6,588). The mean difference was 2,376 (2,182–2,570; p<0.001) for all injectable agents and 1,762 (1,645–1,879; p<0.001) for new injectable agents.

Conclusions: Surrounding the reimbursement incentive increase in 2022, outpatient antineoplastic prescribing increased nationwide for both oral and injectable agents in Japan, particularly among new agents.

Keywords: antineoplastic agents, outpatient cancer treatment, health policy

Introduction: Immunotherapy (IO) has redefined the therapeutic landscape of metastatic non-small cell lung cancer (NSCLC), as reflected across landmark trials. Despite these advances, Chemotherapy remains the cornerstone of treatment for this tumor subtype, particularly in Low-Middle Income Countries (LMICs). The comparative clinical and economic effectiveness among these regimens remains scarce and necessitates real-world evaluation.

Aims: To compare the overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) between IO-based regimens and standard chemotherapy in driver mutation-negative metastatic NSCLC. To evaluate the incremental cost-effectiveness of IO-based treatment.

Methods: This phase IV real-world external comparator study included adult patients with driver mutation-negative metastatic NSCLC and Eastern Cooperative Oncology Group performance status 0–2. Patients received either IO alone or IO combined with chemotherapy (external comparator arm) or standard chemotherapy (control arm). Patient-level external comparator data were obtained from the cBioPortal for Cancer Genomics. Inverse Probability of Treatment Weighting (IPTW) was applied to minimize treatment-selection bias, and survival outcomes were analyzed using adjusted hazard ratios (HRs).

Results: A total of 119 patients were included, with 68 receiving IO-based therapy and 51 receiving chemotherapy. Median OS was significantly longer in the IO arm compared with chemotherapy (26.0 vs 8.5 months; adjusted HR 0.28, 95% CI 0.16–0.49; p<0.001). Median PFS was also improved with IO (10.6 vs 5.4 months; adjusted HR 0.48, 95% CI 0.31–0.71; p<0.001). The ORR was higher in the IO arm than in the chemotherapy arm (42.2% vs 21.3%; p<0.001). The incremental cost-effectiveness ratio for IO was INR 723,615 per additional month of PFS gained.

Conclusions: Immunotherapy-based regimens demonstrated superior survival outcomes compared with standard chemotherapy in driver mutation-negative metastatic NSCLC. Despite these clinical benefits, the high economic burden associated with immunotherapy may limit its accessibility and affordability, particularly in LMIC settings.

Keywords: Non-Small Cell Lung Cancer, Immunotherapy, Cost-effectiveness Analysis

Introduction: Chemotherapy dose modifications commonly occur in clinical practice due to treatment-related toxicities, comorbidities, and disease-related factors. Relative dose intensity (RDI) quantifies delivered chemotherapy intensity relative to the planned regimen. Although reduced RDI has been linked to poorer outcomes in some malignancies, evidence in early breast cancer (EBC) remains inconsistent.

Aims: To characterize the distribution of chemotherapy RDI, patient characteristics and evaluate the association between RDI and clinical outcomes in patients with EBC.

Methods: Utilizing a single-center medical database (2010-2021), patients with EBC who completed first-line chemotherapy were enrolled and stratified into adjuvant or neoadjuvant cohorts according to treatment sequence. RDI was dichotomized using an 85% threshold. Primary outcomes were overall survival (OS) and disease-free survival (DFS) in the adjuvant cohort, and pathological complete response (pCR) in the neoadjuvant cohort. Inverse probability of treatment weighting and landmark analysis were applied to address potential confounding and immortal time bias.

Results: Of 13,374 screened patients, 2,686 were eligible, including 512 (19.1%) with RDI <85%. Patients with RDI <85% were older, with higher prevalence of obesity, renal disease, advanced stages, but lower smoking/alcohol consumption (all P <0.01). In the adjuvant cohort (n=2,397), 468 patients (19.5%) had RDI <85%, which was not significantly associated with OS (aHR 0.78; 95% CI: 0.51-1.19) or 6-year DFS (aHR 0.89; 95% CI: 0.59-1.32). In the neoadjuvant cohort (n=289), 44 patients (15.2%) had RDI <85%, with no significant difference in pCR (aOR 0.65; 95% CI: 0.30-1.41). Sensitivity analyses (80%, 90%, 95% RDI thresholds) and BMI-stratified subgroup analyses yielded consistent results.

Conclusions: Among patients with EBC who completed planned first-line chemotherapy, reduced RDI was not significantly associated with OS, DFS, or pCR. Larger studies are warranted to confirm these findings and evaluate the impact of RDI on safety outcomes.

Keywords: Relative dose intensity, Early breast cancer, Clinical outcomes

Introduction: Immune Checkpoint Inhibitors (ICIs) demonstrate promising efficacy in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC), as reflected across the landmark CHECKMATE-651 and KEYNOTE-048 trials. However, comparative evidence between dual ICI blockade and pembrolizumab monotherapy in patients with high PDL-1 expression remains limited.

Aim: To compare the effectiveness and safety of nivolumab plus ipilimumab versus pembrolizumab monotherapy in PD-L1 CPS >20 R/M HNSCC

Methods: This was an observational, external comparator (EC) study. The patient-level data used for the EC group were accessed via the cBioPortal for Cancer Genomics. Control arm data were obtained from the KEYNOTE-048 trial and adjusted using the Matching-Adjusted Indirect Comparison (MAIC) to align baseline covariates with the EC population. Adult patients with R/M HNSCC who had an ECOG PS of 0-2 and a PD-L1 CPS score >20 were recruited. The patients received either nivolumab plus ipilimumab (EC) or pembrolizumab monotherapy. The primary endpoints were median OS, PFS, and ORR. Safety was the secondary endpoint.

Results: A total of 239 patients were recruited, 106 in the nivolumab plus ipilimumab group and 133 in the pembrolizumab group. The median OS for the nivolumab plus ipilimumab group was 16.3 months (95% CI, 11.9-20.3), compared to 14.64 months (95% CI, 12.10-17.63) for the pembrolizumab group (P=0.04). The median PFS among patients receiving nivolumab plus ipilimumab was 11.0 months (95% CI, 10.61-13.38) compared to 9.3 months (95% CI, 7.62-13.17) in the pembrolizumab group (P=0.08). The ORR was 28.8% in the nivolumab plus ipilimumab arm and 23.3% in the pembrolizumab arm. The rate of grade >3 adverse events were 31% in the nivolumab plus ipilimumab group and 45% in the pembrolizumab group.

Conclusion: Dual ICI blockade demonstrated improved survival outcomes and higher response rates compared with pembrolizumab monotherapy among higher PDL-1 expressing R/M HNSCC patients.

Keywords: Immunotherapy, HNSCC, Cost-effectiveness

Introduction: Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) confer pleiotropic benefits, evidence regarding their association with colorectal cancer (CRC) risk, site-specific effects, and potential mechanisms remains limited and conflicting.

Aims: To assess 5-year incident CRC risk associated with GLP-1 RAs overall and by anatomical site, and explore potential mechanisms.

Methods: We conducted a retrospective cohort study embedded in target trial emulation framework using the TriNetX global dataset. The study included adults with type 2 diabetes and eGFR ≥30 mL/min/1.73 m2 who initiated GLP-1 RAs or dipeptidyl peptidase-4 inhibitors (DPP4i) between 2016 and 2025. We used the propensity score-matching to balance baseline covariates, including demographics, comorbidities, co-medications, laboratory data, colonoscopy history, and healthcare visits. The primary outcomes were 5-year risk of any CRC, right-sided colon cancer, left-sided colon cancer, and rectal cancer. We employed Cox proportional hazard models to generate hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results: After matching, 143,236 matched pairs were included in the analysis. The mean age was 59.40 years, 47.50% were male, and baseline characteristics were balanced between groups. GLP-1 RA use was associated with significantly lower risks of overall CRC (HR, 0.81; 95% CI, 0.73 to 0.90), right-sided CRC (HR, 0.73; 95% CI, 0.60 to 0.88) and left sided CRC (HR, 0.81; 95% CI, 0.70 to 0.94) compared with DPP4i. GLP-1 RA use was also associated with a nonsignificant trend toward a lower risk of rectal cancer (HR, 0.870; 95% CI, 0.720 to 1.050). Lower BMI levels among GLP-1 RA users suggest a potential role of improved weight control in the observed reduction in CRC risk [-3.50 (-9.47%) vs 1.15 (3.64%)].

Conclusions: Our finding suggests that GLP-1 RA initiation is associated with a lower risk of CRC across anatomical sites, evidenced by improvements in weight control.

Keywords: GLP-1 RA, cancer, diabetes

Introduction: Novel oncology medicines often enter the market at high prices despite uncertain clinical benefit, raising concerns about patient management and health-system sustainability. Evidence remains limited on how much real-world consumption and expenditure is accounted for by medicines without European Society for Medical Oncology Magnitude of Clinical Benefit Scale scores (ESMO-MCBS) defined substantial clinical benefit (SCB) across countries.

Aims: We quantified early post-approval drug utilisation for novel oncology medicines and related association with clinical-benefit status.

Methods: We conducted a multinational drug-utilisation study of 53 oncology medicines approved by the FDA or EMA during 2015–2022. Clinical benefit was classified using updated ESMO-MCBS. Using IQVIA MIDAS, a commercial pharmaceutical sales database, we measured two-year post-approval consumption in standard units (SU) and expenditure across 71 countries or regions. In the US and Europe, we used two-part models to assess access, defined as any observed consumption within two years, and uptake, defined as consumption intensity among medicines with observed consumption.

Results: Overall, 37 medicines (69.8%) did not demonstrate substantial clinical benefit (SCB) by ESMO-MCBS. In the US, these medicines accounted for 483.3 SU and US$212,689.4 per 10,000 population, representing 61.0% of consumption and 73.8% of expenditure. Across 27 European countries, corresponding median values were 127.9 SU (interquartile range: 37.6–360.9) and US$11,762.6 (2,280.8–33,649.7), representing 63.0% (48.7–69.8) of consumption and 51.5% (45.2–60.2) of expenditure. Medicines without SCB were associated with lower access (odds ratio 0.59 [95% confidence interval 0.41–0.86]; p=0.006), and lower uptake (consumption ratio 0.42 [0.30–0.58]; p<0.001), corresponding to 58% lower mean uptake.

Conclusions: Across countries, many novel oncology medicines without ESMO-MCBS defined SCB accounted for substantial consumption and expenditure despite lower uptake than drugs with SCB.

Keywords: Oncology medicines, Health technology assessment, Drug utilisation