Expert Review of Anticancer Therapy最新文献

Background: Fruquintinib, a VEGFR1-3 tyrosine kinase inhibitor, is approved for treating refractory metastatic colorectal cancer. Recent clinical practice has shown that combining fruquintinib with programmed cell death protein 1 (PD-1) inhibitors can achieve better efficacy.The objective of this study is to assess the efficacy and safety of combining PD-1inhibitors with fruquintinib.

Methods: We systematically searched PubMed, Cochrane Library, Embase, Wanfang, and CNKI up to 28 August 2024 for studies comparing fruquintinib combined with PD-1 inhibitors to fruquintinib alone. RevMan software was used to perform meta-analyses of survival data for the included studies.

Results: A total of 9 retrospective cohort studies and 1 randomized controlled trial were included, involving a total of 716 patients. Compared with the monotherapy group, the combination therapy group had a greater Overall Response Rate [RR = 2.45,95% CI (1.83, 3.56), p < 0.00001], Disease Control Rate [RR = 1.37,95% CI (1.64,4.79), p = 0.0002], and progression-free survival [HR = 0.64,95% CI (0.49, 0.84), p = 0.001]. However, there was no significant difference in overall survival between the two groups. The incidence of adverse effects was identical in both groups.

Conclusion: Fruquintinib combined with PD-1 inhibitors was more effective than fruquintinib alone in the treatment of advanced colorectal cancer, with acceptable safety.

Registration: PROSPERO (registration number CRD42024583116).

Introduction: Primary effusion lymphoma (PEL) is a rare subtype of B-cell lymphoma primarily affecting immunocompromised and elderly individuals. Given the dismal survival rates associated with traditional treatments, studying novel therapeutic approaches to improve patient outcomes is critical.

Areas covered: This review focuses on developing therapeutic options for PEL that target particular viral and cellular mechanisms involved in PEL pathogenesis. Since the CHOP regimen was associated with a lower median survival rate, alternative treatments, including stem cell transplantation, have also been explored, but have generally produced unsatisfactory results. Therefore, novel therapeutic agents are under investigation, including antiretroviral drugs targeting viral pathways and treatments targeting particular cellular processes, such as DNA damage, epigenetics, apoptotic, and immune-modulatory pathways showing promising outcomes in preclinical and clinical research, increasing PEL treatment efficacy while minimizing toxicity. In this review, we conducted a comprehensive literature search using PubMed, and Google Scholar for studies published between 1989 and 2024.

Expert opinion: Further research is needed to refine the appropriate combination methods and strategies behind drug interactions. Targeted therapies could be investigated further to improve therapeutic efficacy and reduce toxicity in this type of lymphoma.

Introduction: Neoadjuvant immunotherapy is emerging as an effective approach for resectable stage III/IV melanoma, showing improvements in disease response and survival outcomes.

Areas covered: This review summarizes findings from neoadjuvant treatment trials in melanoma patients. Using the PubMed search engine and including the keywords 'neoadjuvant,' 'immunotherapy,' and 'melanoma,' we selected 18 trials that showed efficacy in patients with melanoma, mainly testing checkpoint inhibitors alone or in combination. Across all trials examined, treatments showed objective disease responses, which frequently translated into improved disease-free survival.

Expert opinion: Additional phase III studies comparing neoadjuvant and adjuvant therapies are needed to establish the optimal standard of care. The variety of regimens and dosing schedules investigated highlights the need for further research to determine the most appropriate treatments in this clinical setting. Advances in the study of biomarkers that can identify specific subgroups of patients will guide future research in this field.

Introduction: Tenosynovial giant cell tumor (TGCT) is a rare soft tissue neoplasm with aggressive local growth. The disease is driven by excessive CSF1 expression in tumor cells, leading to increased recruitment of monocytes and macrophages, cytokine production, and tumor development. Targeted therapy against CSF1R is an effective treatment approach for unresectable, symptomatic TGCT. Vimseltinib, a novel, small-molecule tyrosine kinase inhibitor of CSF1R, has shown clinical efficacy in patients with TGCT.

Areas covered: This paper outlines the pathogenesis and therapeutic options for TGCT, along with a detailed profile of vimseltinib, including its mechanism of action, pharmacokinetics, efficacy and safety data from clinical studies. The efficacy and tolerability of vimseltinib are indirectly compared with previously known CSF1R inhibitors.

Expert opinion: In the MOTION study, the use of vimseltinib in patients with advanced TGCT resulted in a high objective response rate, substantial benefit in reducing clinical symptoms (such as pain and stiffness), and a favorable safety profile. Vimseltinib represents a promising new therapeutic option for patients with unresectable TGCT and is currently awaiting regulatory review by the FDA and EMA.

Introduction: For decades, first-line treatment for advanced/metastatic urothelial cancer has been platinum-based chemotherapy. However, many patients do not respond to platinum-based chemotherapy alone, and the vast majority do not have durable responses. While immune checkpoint blockade has demonstrated benefit in this setting, initial trials of concurrent chemotherapy and immune checkpoint blockade did not demonstrate improvements in overall survival.

Areas covered: The recent CheckMate 901 trial compared gemcitabine, cisplatin, plus nivolumab to gemcitabine and cisplatin alone for first-line treatment of advanced/metastatic urothelial cancer. This was the first trial to demonstrate significant benefit in the combined chemotherapy and immune checkpoint blockade arm in advanced/metastatic urothelial cancer, most significantly showing an improvement in the primary outcomes of progression-free survival and overall survival, and the exploratory outcomes of objective response rate, complete response rate, and duration of complete response.

Expert opinion: The combination of gemcitabine, cisplatin, plus nivolumab represents a new first-line treatment option for metastatic urothelial cancer. This article details the clinical benefit observed and how this establishes proof-of-concept for prior hypotheses related to the importance of the specific chemotherapy regimen combined with immune checkpoint blockade, revolving around immunomodulatory mechanisms of action of cisplatin, and synergy of these mechanisms with immunotherapy.

Introduction: Targeted radiopharmaceutical therapies (RPTs) have emerged as a promising approach for the precise treatment of various cancers. Delivering ionizing radiation directly to cancer cells while sparing surrounding healthy tissue, radiopharmaceuticals offer enhanced efficacy and reduced toxicity compared to conventional external beam radiation therapy (i.e. photons and electrons).

Areas covered: In the current era of personalized cancer care, the appropriate choice of RPTs for a clinical condition and the specific patient's care needs to be better understood. Several available RPT agents with their respective clinical applicability along with rapidly ongoing research in this field have now given RPTs the ability to lend themselves to a personalized medicine focus. This review provides an overview of recent advancements in RPT, including nuclide selection and development, molecular targeting strategies, radiopharmaceutical development, and clinical applications.

Expert opinion: We discuss the underlying principles, challenges, and opportunities for future development. Furthermore, we explore emerging technologies and future directions in the field, highlighting the potential impact on personalized cancer care.

Introduction: Neoadjuvant immunotherapy has rapidly evolved as a novel approach in oncology, reshaping the standard treatment for several malignancies, including melanoma, lung, bladder, colorectal, and breast cancer. While it has an acceptable safety profile, challenges persist due to the complexity of the tumor microenvironment (TME), immune evasion, T-cell exhaustion, and identification of biomarkers. Addressing these issues is critical for optimizing treatment regimens, minimizing immune-related adverse events, and ensuring successful clinical integration.

Areas covered: This review explores current research on neoadjuvant immunotherapy, emphasizing its impact on standard of care treatment, efficacy, safety, and clinical challenges. A literature search was conducted using PubMed and ClinicalTrials.gov for studies published in the last 5 years. Ongoing research aims to enhance the efficacy of neoadjuvant immunotherapy, identify resistance mechanisms, and broaden indications. Current clinical trials focus on biomarker-driven patient selection, refining immune response modulation through combination strategies, and developing evidence-based protocols for implementation into routine oncology practice.

Expert opinion: Neoadjuvant immunotherapeutic options have rapidly changed the oncological treatment landscape in only a few years, and this treatment paradigm has quickly become a new standard of care in multiple solid tumors. With continued clinical investigation, neoadjuvant immunotherapy has the dramatic potential to further advance cancer care.

Introduction: Advancements in immunotherapy and angiogenesis-targeted therapies have transformed the upfront treatment of renal cell carcinoma (RCC). However, long-term prognoses for patients with unresectable and metastatic disease often remains limited, with the majority experiencing progression after exposure to front-line therapy. In most cases of relapsed or refractory (R/R) disease after prior exposure to an immune checkpoint inhibitor (ICI), there is no role for ICI-rechallenge. Therefore, treatment of R/R RCC relies on the appropriate selection of therapies targeting growth pathways dependent on vascular endothelial growth factor (VEGF) or hypoxia-inducible factor (HIF).

Areas covered: This review article summarizes the current landscape of targeted therapies for use in second-line or later-line settings for the treatment of clear cell and non-clear cell RCC. Novel therapeutic strategies currently in development are also discussed.

Expert opinion: The treatment of R/R RCC primarily consists of inhibition of VEGF, HIF, and mTOR pathways, and the selection of a specific agent depends on the histologic subtype of the tumor, the prior lines of therapy chosen, and patient co-morbidities. Future tumor-based and circulating biomarker research might one day enable the identification of transcriptional signatures that could predict a response to immune, angiogenesis, or HIF-based therapies.

Background: The objective of this study is to evaluate the correlation between survival outcomes and the modified cachexia index (mCXI) in patients with metastatic breast cancer who have been treated with cyclin-dependent kinase (CDK) 4/6 inhibitors.

Methods: This study was conducted on patients with metastatic breast cancer who received CDK 4/6 inhibitors (either Palbociclib or Ribociclib) between January 2020 and November 2024.

Results: 240 patients were included. A total of 236 patients (98.3%) were female. Median age was 57 (IQR: 48-66 years). The median follow-up period from the initiation of CDK 4/6 inhibitors to the last control was 20 months. One hundred eighty-four patients (76.7%) received ribociclib, while 56 (23.3%) received palbociclib. At diagnosis, 179 patients (74.6%) had metastatic disease. Patients are classified as modified cachexia index-low (mCXI-Low) and mCXI-High according to the receiver operating characteristic (ROC) analysis results for overall survival (OS) prediction [AUC: 0,654 p:<0,001 Cut-off value = 93.5]. Following multivariate analysis, both progression-free survival [HR: 1.50 (95% CI 1.07-2.12), p = 0.02] and overall survival [HR: 3.22 (95% CI 1.90-5.46), p < 0.001] were found to be significantly associated with mCXI.

Conclusion: mCXI is associated with overall survival in metastatic breast cancer patients who are treated with CDK 4-6 inhibitors.