Expert Review of Anticancer Therapy最新文献

Introduction: In the era of precision medicine, molecular biomarker testing is increasingly becoming the standard of care for Non-Small Cell Lung Cancer (NSCLC) patients. Tissue and liquid biopsy-based Next-Generation Sequencing (NGS) is now highly recommended.

Areas covered: Different NGS platforms emerged as a cost-effective strategy to perform a massive and parallel sequencing performing higher technical sensitivity than old generation technologies in detecting low abundant alterations in challenging diagnostic samples. NGS systems can detect single nucleotide variants (SNV), small insertions, and deletions (indels), copy number alterations (CNAs) and structural variants (SVs) or gene fusions across selected druggable genes optimizing clinical administration of NSCLC patients. The diagnostic implementation of the most adequate NGS panel depending on several factors that could impact on the clinical utility of the testing assay.

Expert opinion: Promising advanced technologies are emerging as potentially integrative tools in personalized medicine. In this context, multi-omic evaluation including genomic, transcriptomic, fragmentomic and epigenomic signatures are under investigation to significantly modify clinical algorithms of NSCLC patients. On this basis, sequencing strategies may play a pivotal role in the implementation of a new predictive model for cancer diagnosis and prognosis.

Introduction: Patients with advanced/metastatic non-small cell lung cancer (NSCLC) and programmed death ligand-1 (PD-L1) tumor cell expression <1% are difficult to treat, and an optimal treatment strategy for these patients is yet to be defined.

Areas covered: There have been significant advances in immunotherapy for NSCLC in the past decade. This article aims to answer the question of the optimal first-line treatment for patients with advanced/metastatic NSCLC and PD-L1 expression <1%, based on efficacy and safety data from phase 3 studies (published up to 31 December 2024).

Expert opinion: Current evidence from subgroup and exploratory analyses of phase 3 studies and indirect comparisons suggest that PD-1/PD-L1 inhibitors (with or without chemotherapy) combined with a cytotoxic T lymphocyte-associated protein-4 inhibitor or antiangiogenic therapy may provide the highest progression-free survival (PFS) and overall survival (OS) benefits in patients with newly diagnosed advanced/metastatic NSCLC and PD-L1 tumor cell expression <1%. Of these regimens, dual immunotherapy with nivolumab and ipilimumab combined with chemotherapy appeared to offer some advantages in terms of OS, PFS, objective response rates, and duration of response, relative to other treatment approaches. Well-designed, comparative studies are warranted to more definitively determine the best first-line treatment for these patients.

Background: Peritoneal recurrence challenges pediatric solid tumors. HIPEC is established in adults but pediatric evidence is limited. We assessed safety and preliminary efficacy of intraoperative HIPEC in children.

Research design and methods: Retrospective study of 100 children (Aug 2020-Jan 2024) undergoing cytoreductive surgery (CRS) plus HIPEC (cisplatin, doxorubicin, or ifosfamide at 40.5-41.5°C for 60 min). Outcomes included complications, recurrence, and survival.

Results: The median peritoneal carcinomatosis index was 4.0 (IQR: 8.0), and complete cytoreduction (CC-0) was achieved in 96% of patients. Adverse events were primarily grade 1-2 gastrointestinal toxicity (90%) and myelosuppression (93%); grade 3 events occurred in 10% and 7%, respectively. No grade 4+ adverse events or 30-day mortality were observed. Transient liver enzyme elevation (49%) normalized within one month. At a median follow-up of 24.3 months, the median overall and progression-free survival were 25.2 and 24.6 months, respectively. Seven patients experienced recurrence recurred and ten died.

Conclusions: HIPEC demonstrated low rates of severe complications and promising survival outcomes. The main limitations include the retrospective design and tumor heterogeneity. Therefore, Large-scale prospective studies are warranted to validate these findings.

Introduction: This review critically appraises recent clinical and translational advances on ropeginterferon alfa-2b, a long-acting, mono-pegylated interferon that has become a key therapeutic option for polycythemia vera (PV). Beyond its cytoreductive efficacy, ropeginterferon exerts immunomodulatory and antiproliferative effects that may modify disease biology. The review outlines its therapeutic rationale, pharmacologic profile, and emerging role as a disease-modifying agent compared with conventional cytoreductive therapies.

Areas covered: This article summarizes the pharmacokinetic properties, clinical efficacy, molecular activity, and safety of ropeginterferon alfa-2b across pivotal trials and real-world studies. Particular attention is given to hematologic responses, reduction of JAK2 V617F allele burden, and long-term tolerability. Data were identified through a systematic search of PubMed, Embase, and ClinicalTrials.gov for English-language studies published up to 2025.

Expert opinion: Ropeginterferon alfa-2b has redefined PV management by combining durable hematologic control with progressive molecular remission. Its favorable efficacy-toxicity balance and convenient dosing support long-term use, particularly in younger or treatment-naïve patients. Future research should refine patient selection, explore predictive biomarkers, and define its role among disease-modifying agents capable of transforming PV into a chronic, potentially controllable disorder.

Introduction: Targeted therapy is an established treatment strategy for biliary tract cancer (BTC), yet its clinical efficacy remains limited when compared to promising in vitro and in vivo findings. This highlights the translational gap between preclinical research and real-world patient outcomes, emphasizing the urgent need for improved strategies to bridge laboratory insights with clinical practice.

Areas covered: This report explores the heterogeneous landscape of targeted therapy in BTC. It reviews established facts, including molecular mechanisms, signaling pathways, and clinical trial data, while addressing uncertainties such as patient- and tumor-related variables and infectious comorbidities. In addition, it discusses current demands and future challenges, with emphasis on integrating novel technologies, biomarker-driven approaches, and multidisciplinary collaborations to enhance therapeutic precision.

Expert opinion: Early and accurate diagnosis remains the cornerstone of successful BTC treatment. Noninvasive biomarkers, particularly liquid biopsy platforms, hold promise for improving detection and monitoring. Clinically, the establishment of high-volume BTC centers with integrated scientific and medical expertise is essential to translate molecular analyses into personalized therapies. Moreover, systematic incorporation of BTC-related clinical and molecular data into international multicenter trials is imperative. Such integration will refine therapeutic paradigms, accelerate drug development, and foster innovation through strategic collaborations with pharmaceutical industry consortia.

Introduction: Urothelial carcinoma (UC) is a highly aggressive malignancy that has traditionally been treated with platinum-based chemotherapy. In recent years, the therapeutic landscape has undergone substantial transformation with the advent of precision oncology, particularly through the introduction of immune checkpoint inhibitors, targeted agents, and antibody-drug conjugates (ADCs).

Areas covered: We searched MEDLINE (via PubMed), Embase, and ClinicalTrials.gov and reviewed practice guidelines from ASCO, ESMO, AIOM, and EAU in order to describe the current landscape of ADC-based therapy in UC.

Expert opinion: ADCs are rising as a cornerstone in UC, but important challenges remain. Future perspectives point toward the development of combination strategies and next-generation ADCs, designed to overcome resistance, minimize toxicity, and enhance selectivity.

Introduction: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy have markedly improved clinical outcomes and are the preferred first-line treatment for metastatic hormone receptor - positive breast cancer. However, acquired resistance is almost universal, leading to a critical need for effective strategies in the post-CDK4/6i setting.

Areas covered: This review summarizes therapeutic approaches investigated after progression on CDK4/6i plus endocrine therapy. Key therapeutic approaches in this setting focus on overcoming resistance by inhibiting pathways such as PI3K/AKT/mTOR, altering treatment class through switching CDK4/6 inhibitors or endocrine therapy agents, and incorporating selective estrogen receptor degraders (SERDs). In addition, several novel strategies are under investigation, including targeting CDK7, utilizing antibody - drug conjugates, and exploiting DNA repair vulnerabilities with poly (ADP-ribose) polymerase (PARP) inhibitors. We conducted a literature search in PubMed/MEDLINE, Embase, and Scopus for studies published between January 2018 and June 2025 to identify evidence on efficacy, safety, and patient selection in this setting.

Expert opinion: Therapeutic development for post-CDK4/6i metastatic HR+ breast cancer is evolving rapidly. Identifying molecular drivers of resistance and matching patients to targeted therapies will be essential to optimize outcomes. Continued efforts toward biomarker-based treatment selection and rational sequencing strategies are expected to refine post-CDK4/6i management.

Background: To investigate the impact of baseline and temporal changes of the CT-body compositions on survival in patients with colorectal liver metastases (CLRM) undergoing intra-arterial treatment.

Research design and methods: A total of 146 patients with CLRM (mean age:59.98 ± 11.94, M/F:90/56) who underwent intra-arterial procedures between January-2012 and December-2022 were included. We determined the patient CT-body compositions by measuring at the level of L3 vertebrae on CT scans. The relationship between body composition and survival was evaluated using Kaplan-Meier survival curves, while factors affecting survival were investigated through univariate and multivariate Cox-regression analyses.

Results: Patients with sarcopenia had significantly shorter PFS (median PFS: 2.37 vs. 5.67 months; p < 0.001) and OS (median OS:6.20 vs. 13.47 months; p < 0.001) compared with those without sarcopenia. Similarly, patients with myosteatosis showed shorter PFS (median PFS: 3.73 vs. 6.10 months; p = 0.036) and OS (median OS: 8.80 vs. 15.37 months; p < 0.001) compared to those without myosteatosis. However, there was no statistically significant association between subcutaneous/visceral adipose tissue and survival. Besides other clinical or laboratory parameters, sarcopenia (HR: 2.65, p = 0.006), myosteatosis (HR: 2.74, p = 0.001) and greater loss of skeletal muscle index (HR: 2.03, p = 0.037) were independently associated with decreased overall survival.

Conclusions: Baseline sarcopenia, myosteatosis, and greater loss of skeletal muscle index are independent predictors of poor survival in patients with CRLM undergoing intra-arterial treatment.

Background: Patients with advanced EGFR-mutant NSCLC and high PD-L1 expression (TPS ≥50%) typically respond poorly to EGFR-TKI monotherapy. We compared EGFR-TKI plus chemotherapy versus TKI alone in this population.

Research design and methods: This retrospective study included 212 patients receiving first-line osimertinib with chemotherapy (n = 98) or as monotherapy (n = 114). Primary endpoint was progression-free survival (PFS).

Results: Combination therapy significantly improved median PFS overall (22.5 vs 13.8 months; HR = 0.513, 95% CI:0.372-0.803; p < 0.001) and in PD-L1-high patients (18.2 vs 7.9 months; HR = 0.356, 95% CI:0.195-0.641; p = 0.001). ORR was higher with combination therapy (67.3% vs 36.8%; p < 0.001). Grade ≥3 adverse events were more common with combination therapy (45.9% vs 22.8%) but were primarily manageable hematological events.

Conclusions: Osimertinib-chemotherapy combination showed superior efficacy versus monotherapy in EGFR-mutant, PD-L1-high NSCLC, with manageable safety. Our real-world findings validate and extend the FLAURA2 results by highlighting this high-risk subgroup as one that may derive particular benefit from first-line combination therapy.