Several clinical trials have explored the efficacy and safety of Poly (ADP-ribose) polymerase (PARP) inhibitors in endometrial cancer (EC). However, evidence supporting PARP inhibitors alone or in combination with other medications in advanced or recurrent EC remains limited.

Programmed death (ligand) 1 inhibitors (e.g., avelumab, pembrolizumab, and retifanlimab) are first-line treatment options for patients with locally advanced or metastatic Merkel cell carcinoma (MCC). In the absence of comparative and randomized trials, we aimed to systematically identify and synthesize real-world evidence (RWE) on the effectiveness and safety of immunotherapies in patients with advanced MCC.

Locally advanced or metastatic penile cancer (LA/mPC) is an aggressive and rare malignancy with limited treatment options. While promising, the role of Immune Checkpoint Blockade (ICB) in LA/mPC remains controversial. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of ICB in patients with LA/mPC. A literature search was conducted in PubMed, Embase, and Cochrane (up to June 2025). The analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (CRD420251070583). Proportional outcomes were pooled using a random-effects proportional meta-analysis, and hazard ratios (HR) were pooled using a random-effects model. We used the available Kaplan-Meier curves to recreate time-to-event data from the studies considered. Heterogeneity between studies was evaluated using the I2 metric and Cochran's Q test. A total of 12 cohorts (488 patients) were included in the analysis. The pooled Objective Response Rate in patients treated with ICB was 34.13% (95% CI, 20.62%-56.48%). Subgroup analysis demonstrated marked variability by treatment strategy, with an ORR of 60.7% for ICB plus chemotherapy versus 16.7% for ICB monotherapy (P < .01). At 12 months, pooled Progression-Free Survival (PFS) and Overall Survival (OS) rates were 62.64% (95% CI, 55.55%-70.63%) and 80.21% (95% CI, 74.11%-86.83%), respectively. The median PFS and OS were 5.7 months and 13.6 months, respectively. The pooled incidence of Immune-related Adverse Events was 40.36% (95% CI, 26.82%-60.74%) for any grade and 13.79% (95% CI, 7.67%-24.80%) for grade ≥ 3 events. ICB, particularly when combined with chemotherapy, shows signals of clinical activity in LA/mPC. However, due to high inter-study variability and the single-arm nature of the analysis, these findings are hypothesis-generating and require prospective, randomized, biomarker-driven validation.

The addition of programmed cell death protein-1 (PD-1) inhibitors to chemotherapy (CT) or anti-CTLA4 (ipilimumab) has recently emerged as an effective first-line (1L) treatment for esophageal squamous cell carcinoma (ESCC), the most common form of esophageal cancer globally.

Clinical trials have demonstrated favorable outcomes with sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC). However, significant differences between trial settings and routine clinical practice raise concerns about the real-world prognosis of patients with mTNBC. To address this gap, we conducted the first comprehensive single-arm meta-analysis integrating clinical trials and real-world studies (RWSs) to evaluate clinical outcomes and treatment experiences in mTNBC patients receiving SG.

This study aimed to evaluate whether the Cancer and Aging Research Group (CARG) score is suitable for assessing chemotherapy toxicity risk in older adults with cancer.

Fever in neutropenia (FN) is a potentially lethal complication of chemotherapy for cancer. Prompt administration of broad-spectrum antibiotics is standard of care. Despite conflicting results on the association of time to antibiotics (TTA) with outcomes, TTA limits are used as FN quality measure both in adult and pediatric oncology. This individual patient data (IPD) meta-analysis studied the association between TTA and outcomes in pediatric patients with FN.

The administration of bevacizumab, ramucirumab, and aflibercept increases the incidence of hypertension; however, the risk of discontinuation of cancer therapy due to hypertension from these medications remains unclear. A systematic review and meta-analysis were conducted to assess the incidence and risk of hypertension associated with bevacizumab, ramucirumab, and aflibercept, as well as the risk of treatment discontinuation due to hypertension. Phase III randomized controlled trials (RCTs) of these therapies published through November 5, 2024, were identified through searches in PubMed, Cochrane Library, and Web of Science databases. The meta-analysis included 57 RCTs comprising 34,145 patients who received bevacizumab, ramucirumab, or aflibercept. The overall incidence of hypertension was 28% (95% confidence interval [CI]: 22-34%) for all-grade hypertension and 9% (95% CI: 7-11%) for grade ≥3 hypertension. Compared to control groups, treatment with these agents was associated with an increased risk of all-grade hypertension (odds ratio [OR]: 4.5; 95% CI: 3.7-5.5) and grade ≥3 hypertension (OR: 5.0; 95% CI: 4.0-6.3). The incidence of treatment discontinuation due to hypertension was 1% (95% CI: 1-2%), with a risk difference of 1.60% (95% CI: 0.76-2.38). VEGF inhibitor therapy-induced hypertension has been suggested to increase the risk of cancer treatment discontinuation. Therefore, careful monitoring and management of blood pressure in patients receiving these agents is essential.

Ovarian cancer is one of the most lethal malignancies affecting women, often diagnosed at advanced stages. Bevacizumab, a novel therapeutic agent, has recently demonstrated efficacy in the management of this disease. However, its use has been associated with various adverse effects reported in clinical trials. This systematic review and meta-analysis aimed to provide a comprehensive evaluation of urinary complications linked to bevacizumab therapy in ovarian cancer patients.

Leukemias are heterogenous hematologic malignancies broadly classified into myeloid and lymphoid lineages, each with distinct molecular and clinical features. Here we aime to identify lineage-specific molecular vulnerabilities in myeloid and lymphoid leukemias and use them to guide targeted therapy and rational drug repurposing.

Glioblastoma (GB) is the most common and aggressive malignant brain tumor in adults, with poor long-term survival despite standard treatment. Targeted therapies such as immune checkpoint inhibitors (ICIs) and mTOR inhibitors have been explored to improve outcomes, but their clinical benefit in GBM remains unclear. We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating the efficacy and safety of ICIs and mTORi in adult patients with newly diagnosed or recurrent GB. Databases searched included PubMed, Cochrane Library, and Semantic Scholar through March 2025. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were extracted or estimated and pooled using a fixed-effect model. Risk of bias was assessed with the Cochrane tool. Twenty-one trials involving 2,130 patients were included (12 on ICIs, 9 on mTOR inhibitors). ICIs showed no significant OS benefit (HR: 1.10; 95% CI: 0.98-1.24; p = 0.10), but a modest improvement in PFS (HR: 1.17; 95% CI: 1.04-1.33; p = 0.01). Pembrolizumab in a neoadjuvant setting demonstrated the most favorable outcomes. In contrast, mTOR inhibitors were associated with significantly worse OS (HR: 1.43; 95% CI: 1.08-1.89; p = 0.01), and no PFS benefit (HR: 1.16; 95% CI: 0.89-1.51). ICIs were commonly associated with immune-related adverse events, while mTOR inhibitors showed hematologic and metabolic toxicities. Neither ICIs nor mTOR inhibitors consistently improved survival in unselected GB populations. However, tailored approaches based on molecular features or delivery methods may offer benefits and should be further investigated.

Immune checkpoint inhibitors (ICIs) combined with radiotherapy (RT) enhance antitumor efficacy; however, the optimal sequencing of these treatments remains undefined. We conducted a network meta-analysis (NMA) of randomized controlled trials to compare the efficacy and safety of ICIs administered after completion of RT versus those administered concurrently with RT.

Despite the established role of anti-vascular endothelial growth factor (anti-VEGF) agents as first-line therapy for diabetic macular edema (DME), their therapeutic effect may be incomplete or unsustained in a proportion of patients.

Intra-arterial chemotherapy (IAC) has emerged as a targeted alternative to intravenous chemotherapy (IVC) for retinoblastoma; however, the comparative effectiveness and safety of these approaches remain incompletely defined. We performed a systematic review and meta-analysis to evaluate whether IAC-based regimens are associated with improved clinical outcomes compared with IVC in pediatric retinoblastoma. Twelve studies were included. Comparative studies contributed to the quantitative synthesis, whereas selected non comparative IAC series were summarized qualitatively to provide contextual evidence. Overall survival demonstrated a consistent association favoring IAC across both early and advanced disease categories, with a pooled effect estimate of OR 4.72 (95% CI 2.69-8.28). In early-stage disease, the pooled OR was 12.61 (95% CI 3.82-41.58), while advanced-stage disease showed a pooled OR of 3.56 (95% CI 1.88-6.74). Heterogeneity was negligible within subgroups (I² = 0%). Event-free survival favored IAC-based treatment overall with a pooled RR of 1.36 (95% CI 1.13-1.62). When stratified by treatment approach, IAC alone showed a pooled RR of 1.30 (95% CI 1.01-1.66) with moderate heterogeneity (I² = 61%), whereas IAC combined with IVC sequencing demonstrated a pooled RR of 1.43 (95% CI 1.10-1.86) with no heterogeneity (I² = 0%). Globe salvage outcomes were improved with IAC, with a pooled RR of 1.33 (95% CI 1.23-1.42; I² = 9%). Avoidance of enucleation also favored IAC overall, with a pooled RR of 1.69 (95% CI 1.34-2.12). Subgroup analyses indicated a modest and non-significant effect in early-stage disease (RR 1.27, 95% CI 0.89-1.80) and a clearer effect in advanced-stage disease (RR 2.08, 95% CI 1.54-2.80), with minimal heterogeneity (I² = 0%). Metastatic events were rare across studies; nevertheless, pooled analysis suggested lower odds of metastasis in IAC-based regimens compared with IVC (OR 0.42, 95% CI 0.19-0.91; I² = 0%), with no evidence of subgroup differences between IAC alone and IAC plus IVC sequencing. In conclusion, IAC-based strategies were associated with favorable outcomes in survival, disease control, globe salvage, and avoidance of enucleation compared with IVC, with consistently low heterogeneity across major endpoints and metastatic events remaining uncommon in both arms. These findings support the role of IAC as an important component of contemporary retinoblastoma management, particularly in settings with appropriate technical expertise and multidisciplinary resources.

Intravesical bacillus Calmette-Guérin (BCG) therapy remains the cornerstone for high-risk non-muscle-invasive bladder cancer (NMIBC), but up to 40% of patients experience disease recurrence or progression within 2 yr. We conducted a systematic review and meta-analysis of three phase 3 randomized trials POTOMAC, CREST, and ALBAN; n = 2590) in BCG-naïve high-risk NMIBC disease treated with a combination of BCG and an immune checkpoint inhibitor (ICI). Overall risk of bias was low for all studies. Combination therapy with BCG maintenance was associated with better event-free survival (EFS) in comparison to BCG alone (pooled hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.60-0.99; Q = 3.29, p = 0.2). Using the HR for high-grade recurrence from ALBAN, the pooled estimate was directionally consistent, but not statistically significant (HR 0.78, 95% CI 0.58-1.04; Q = 3.94, p = 0.1). Overall survival was comparable between groups (HR 0.92, 95% CI 0.67-1.26). Grade ≥3 treatment-related adverse events were more frequent with combination therapy (risk ratio [RR] 3.66, 95% CI 2.56-5.24 for BCG induction only; RR 3.97, 95% CI 2.54-6.21 for BCG induction + maintenance). There was a moderate decline in patient-reported quality of life in the ICI + BCG maintenance arms. These findings are supported by moderate-certainty evidence for EFS. BCG monotherapy remains the benchmark for BCG-naïve high-risk NMIBC. ICI addition improves EFS but increases high-grade toxicity, which should prompt cautious and individualized adoption pending mature survival data.

Personalized escalation and de-escalation of immune checkpoint inhibitor (ICI) regimens may help to overcome upfront resistance and mitigate the risk for immune-related adverse events (irAEs). Here, we examined the association between pathological response and irAEs per ICI regimen. Meta-analysis of neoadjuvant ICI trials in melanoma illustrated a pattern of increased toxicity and efficacy with the addition and/or higher dosing of anti-CTLA-4 to anti-PD-1. We subgrouped anti-PD-1, low-dose anti-CTLA-4 + anti-PD-1, high-dose anti-CTLA-4 + anti-PD-1, and anti-PD-1 + anti-LAG-3 cohorts according to the baseline interferon-gamma (IFN-γ) signature and analyzed these for response and toxicity rates. Whereas in IFN-γ high subgroups the addition of (high-dose) anti-CTLA-4 increased toxicity but not efficacy, the addition of high-dose anti-CTLA-4 to anti-PD-1 increased efficacy in the IFN-γ low subgroup, while toxicity remained low. Our findings suggest that baseline immune signatures may be used to separate risk for toxicity from risk for non-response, with implications for patient stratification and treatment regimens.

Pre-therapeutic UGT1A1 genotyping is increasingly performed in patients receiving irinotecan, as its active metabolite SN-38 is primarily cleared through UGT1A1-mediated glucuronidation. Patients with the UGT1A1*28/*28 genotype exhibit reduced UGT1A1 activity, leading to increased SN-38 exposure and a higher risk of adverse events such as neutropenia and diarrhea. Although sacituzumab govitecan contains the same active metabolite as irinotecan, routine UGT1A1 genotyping prior to treatment with this drug is not yet standard practice and is not included in its product information. The aim of this study was to assess whether pre-therapeutic UGT1A1 genotyping may also benefit patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative and triple-negative breast cancer who are treated with sacituzumab govitecan. A literature search was conducted to identify relevant studies assessing the impact of UGT1A1 genotyping on the safety and efficacy of sacituzumab govitecan treatment. A meta-analysis was performed on selected studies. Additionally, a pharmacological analysis was performed using public data comparing SN-38 levels in patients treated with sacituzumab govitecan to those receiving irinotecan. The meta-analysis shows that grade ≥ 3 adverse events, including neutropenia, febrile neutropenia, and diarrhea, occurred more frequently in patients with the *28/*28 genotype. Furthermore, a statistically significant increased risk was found for developing grade ≥ 3 diarrhea or febrile neutropenia in this group. Although the meta-analysis was underpowered due to small sample sizes, the pharmacological analysis demonstrated higher SN-38 levels in patients treated with sacituzumab govitecan, supporting the rationale for UGT1A1 genotyping in this context.

The cell surface protein TROP-2 is overexpressed in various solid tumors, making it an attractive therapeutic target. Datopotamab deruxtecan (Dato-DXd) is a novel antibody-drug conjugate (ADC) designed to selectively deliver cytotoxic agents to TROP-2-expressing cancer cells. It has recently been approved for treating unresectable or metastatic hormone receptor-positive, HER2-negative breast cancer. While preclinical and early phase clinical trials have shown promising efficacy, this meta-analysis aims to provide a comprehensive evaluation of the efficacy and safety of Dato-DXd in patients with advanced solid tumors by synthesizing the available clinical evidence.

This review aims to explore the potential of Indonesian medicinal plants as therapeutic agents for breast cancer in in vitro studies.

Osteosarcoma is an aggressive bone cancer primarily affecting children and adolescents, with low survival rates in advanced stages. A systematic review and meta-analysis were conducted following PRISMA guidelines to evaluate the impact of ICIs on survival and toxicity in advanced osteosarcoma. ICIs show potential in treating advanced osteosarcoma but are associated with significant toxicity and uncertain survival benefits. Further research is needed to define their role and identify biomarkers for predicting response. Close monitoring for adverse events is essential.