The phase 3 KEYNOTE-522 study in high-risk early-stage triple-negative breast cancer (TNBC) showed significantly improved efficacy outcomes with neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab versus neoadjuvant chemotherapy alone. We present findings from the KEYNOTE-522 Japan subgroup. Eligible participants (aged ≥ 18 years) with untreated locally advanced TNBC (stage T1c N1-2 or T2-4 N0-2) were randomized 2:1 to neoadjuvant pembrolizumab 200 mg or placebo plus chemotherapy every 3 weeks for 8 cycles followed by surgery and adjuvant pembrolizumab or placebo for ≤ 9 cycles. Primary endpoints were pathologic complete response (pCR; ypT0/Tis ypN0) at the time of surgery and event-free survival (EFS). Of 76 participants enrolled in Japan, 45 were randomized to the pembrolizumab arm and 31 to the placebo arm. Median time from randomization to data cutoff (March 22, 2024) was 76.3 months. Twenty-four participants (53%) in the pembrolizumab arm and 15 (48%) in the placebo arm achieved pCR (between-treatment arm difference, 4.9%; 95% CI, -17.6% to 27.1%); findings were similar regardless of PD-L1 expression. Rates of EFS at 60 months were 84% and 73%, respectively (HR, 0.54; 95% CI, 0.20-1.50). Grade 3 or 4 treatment-related AEs occurred in 37 of 45 participants (82%) treated with pembrolizumab and 23 of 30 participants (77%) treated with placebo; there were no grade 5 AEs. In conclusion, neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab showed improved efficacy outcomes and manageable safety versus neoadjuvant chemotherapy alone in Japanese participants, supporting the use of this regimen in Japanese patients with high-risk early-stage TNBC. Trial Registration: The study (ClinicalTrials.gov, NCT03036488) was conducted in compliance with local and/or national regulations and International Council for Harmonization Good Clinical Practice guidelines and in accordance with the ethical principles originating from the Declaration of Helsinki.
The oncologic outcomes of pedunculated-type T1 colorectal cancer (CRC) remain unknown. We determined the risk factors for lymph node metastasis (LNM) and recurrence and evaluated the survival according to the treatment method. In this multicenter retrospective study involving 4673 patients with T1 CRC, we analyzed 444 patients with pedunculated-type T1 CRC treated between 2009 and 2016. Treatment included local resection (LR) alone (n = 169), surgery with lymph node (LN) dissection alone (n = 83), and LR followed by additional surgery with LN dissection (n = 192). Factors associated with LNM and recurrence, relapse-free survival (RFS) and overall survival (OS) by treatment were analyzed. The median follow-up period was 64 months. LNM and recurrence were observed in 25 (5.6
Although small bowel bleeding is a known cause of acute lower gastrointestinal bleeding (ALGIB), its outcomes compared to colorectal bleeding remain underexplored. This study aimed to identify baseline characteristics and short- and long-term outcomes associated with small bowel bleeding in comparison to colorectal bleeding. This nationwide retrospective cohort study, based on CODE BLUE-J study, involved 10,342 patients hospitalized for ALGIB. Among 195 patients (2.8%) with acute small bowel bleeding, significant associations were observed with laboratory parameters (e.g., low hemoglobin, platelets, and albumin), clinical signs (e.g., tarry stool), and medical history, compared to 6832 patients with colorectal bleeding. Multivariate regression analysis showed no significant difference in 30-day rebleeding or mortality between small bowel and colorectal bleeding. However, small bowel bleeding was associated with higher transfusion volume, lower endoscopic treatment rate, higher rates of interventional radiology and surgery, and longer hospital stay (all p < 0.005). While long-term cumulative rebleeding rates were similar, cumulative mortality was significantly higher in the small bowel bleeding group (p < 0.001). This large-scale endoscopic study revealed differences in several clinical factors at presentation and in short- and long-term outcomes between small bowel and colorectal bleeding. These findings underscore importance of identifying small bowel bleeding in ALGIB.
Background: With the growing older adult population in developed countries, the number of older adults with cancer is also rising. Selecting appropriate treatments for these patients is challenging, owing to difficulties in assessing their tolerance to invasive surgery. This study aimed to identify the prognostic factors in octogenarians undergoing first-time hepatectomy for hepatocellular carcinoma (HCC). Methods: We enrolled 229 consecutive patients with resected HCC between 2008 and 2018, excluding three who died within 90 days post-surgery. Univariate and multivariate analyses were performed to identify variables associated with overall survival (OS) and recurrence-free survival (RFS). Results: Participants were aged 80–93 years and included 163 males and 63 females, with the majority having hepatitis C virus. Liver function was well-preserved (Child–Pugh grade A: 215; grade B: 12). Laparoscopic hepatectomy was performed in 34 patients. The following factors showed significant association with OS in the univariate analysis: age-adjusted Charlson comorbidity index (ACCI) ≥ 10, neutrophil-to-lymphocyte ratio ≥ 3, alpha-fetoprotein (AFP) > 100 ng/mL, tumor size > 50 mm, and multiple tumors. Multivariate analysis confirmed ACCI ≥ 10, AFP > 100 ng/mL, tumor size > 50 mm, and multiple tumors as independent risk factors for OS. Regarding RFS, the significant factors identified in the univariate analysis included sex, indocyanine green retention rate at 15 min > 10%, des-gamma-carboxy prothrombin > 500 mAU/mL, intraoperative bleeding, tumor size, multiple tumors, and vascular invasion. Multivariate analysis identified sex, multiple tumors, and vascular invasion as independent risk factors for RFS. Conclusions: Elevated tumor markers, multiple tumors, and ACCI ≥ 10 are risk factors for poor OS in older adults with primary HCC. Both tumor-related factors and ACCI score should be considered when selecting treatment for octogenarian patients with HCC.
OBJECTIVES:To compare the real-world effectiveness and safety of pembrolizumab plus lenvatinib with axitinib-based regimens (avelumab plus axitinib or pembrolizumab plus axitinib) as first-line therapy for metastatic clear cell renal cell carcinoma. METHODS:We retrospectively analyzed 107 patients treated with immuno-oncology plus vascular endothelial growth factor inhibitor combinations between 2017 and 2025. Propensity score matching (1:1, 0.2 caliper) generated 42 matched pairs. Objective response rate, progression-free survival, overall survival, and adverse events were assessed. Multivariable logistic regression and Cox regression analyses were performed in the overall cohort, and conditional logistic regression and stratified Cox regression analyses were applied in the matched cohort. RESULTS:In the matched cohort, pembrolizumab plus lenvatinib demonstrated a significantly higher objective response rate than axitinib-based regimens. The incidence of any-grade and grade ≥ 3 adverse events was similar between regimens. However, pembrolizumab plus lenvatinib was associated with higher rates of hypertension (including grade ≥ 3 hypertension), fatigue, appetite loss, and rash in the full-dose subgroup. Progression-free and overall survival did not differ significantly. Multivariate analyses identified pembrolizumab plus lenvatinib treatment as an independent predictor of objective response, whereas survival outcomes were associated with clinical factors rather than the regimen type. CONCLUSIONS:Pembrolizumab plus lenvatinib achieved a superior tumor response to axitinib-based regimens, whereas survival outcomes were comparable. Treatment selection should balance enhanced antitumor activity with differences in toxicity profiles.
