Expert Review of Anticancer Therapy最新文献

Background: Currently, the choice between radiotherapy and surgery for treating older patients with early laryngeal cancer remains unclear. The aim of this retrospective study is to investigate the therapeutic patterns and survival outcomes for a cohort of older patients with early laryngeal cancer who received radiation therapy (RT) or surgery.

Methods: Clinical records of 1833 patients aged 65+ with stage I/II laryngeal cancer from the SEER registry (2010-2015) were assessed. Of these, 1319 underwent RT and 514 had surgery alone. Kaplan-Meier analysis assessed overall survival (OS) and cancer-specific survival (CSS), with Log-rank tests for comparison.

Results: The 5-year OS and CSS rates were 61.1% and 80.6%, respectively. Univariate analysis showed age, gender, T stage, histology, and treatment as prognostic factors for OS and CSS. Multivariate analysis linked age, T stage, and treatment to OS, and gender, histology, T stage, and treatment to CSS. Surgery improved OS and CSS for most early-stage patients, except those with grade III cancer.

Conclusion: Among early-stage laryngeal cancer patients aged 65 years or older reported in the SEER database, those treated with surgery experienced longer OS and CSS compared to those treated with RT, except for patients with grade III.

Introduction: The synergistic combination of histone deacetylase inhibitors and platinum-based medicines represents a promising therapeutic strategy to efficacy and overcome drug resistance in cancer therapy, necessitating a comprehensive understanding on their molecular interactions and clinical potential.

Areas covered: The objective of presented review is to investigate the molecular pathways of platinum medicines and HDAC inhibitors. A comprehensive literature review from 2011 to 2024 was conducted across multiple databases like MEDLINE, PubMed, Google Scholar, Science Direct, Scopus and official websites of ClinicalTrial.gov to explore publications on HDAC inhibitors, platinum drugs, and combination cancer therapies, revealing preliminary evidence of innovative treatment strategies involving HDAC inhibitors and platinum chemotherapeutics. Several new platinum (IV) complexes, with HDAC inhibitory moieties and better cytotoxicity profiles than conventional platinum drugs, are also reviewed here.

Expert opinion: The above combination has great potential in cancer treatment, however managing toxicity, dosage regimens, and patient selection biomarkers are problematic. More selective HDAC inhibitors and innovative delivery techniques are potential areas for future research. An adaptation toward changing cancer therapeutic landscapes, highlights combining HDAC inhibitors with platinum-based medicines serves as a new concept for personalized medicine, however, a deeper research is still needed at this time.

Introduction: Immuno-oncology (IO) therapies have become integral to renal cell carcinoma (RCC) management, RCC remains a complex malignancy with diverse clinical behaviors and a heterogeneous tumor microenvironment, highlighting the need for predictive biomarkers to optimize therapy.

Areas covered: This review synthesizes recent findings from clinical trials, translational studies, and molecular analyses to provide an updated perspective on biomarker research for IO therapies in RCC. A literature search was conducted using PubMed, Embase, and Web of Science for articles published between January 2010 and November 2024.

Expert opinion: IO combination therapies have demonstrated significant improvements in progressionfree survival and overall survival compared with sunitinib. However, treatment outcomes vary according to the IMDC risk groups, metastatic sites, and histological subtypes, such as sarcomatoid differentiation. Advances in molecular biology have elucidated the roles of genetic alterations and immune phenotypes in modulating IO efficacy. Emerging biomarkers, including tertiary lymphoid structures, human endogenous retroviruses, and the gut microbiome, show promise but require further validation. Addressing challenges such as intratumoral heterogeneity and dynamic immune responses will be key to identifying actionable biomarkers. Continued integration of clinical and molecular insights is essential for improving patient selection and outcomes in RCC treated with IO therapies.

Introduction: BRAF mutations are the most common driver mutation in cutaneous melanoma, present in 40% of cases. Rationally designed BRAF targeted therapy (TT) has been developed in response to this, and alongside immune checkpoint inhibitors (ICI), forms the backbone of systemic therapy options for BRAF-mutant melanoma. Various therapeutic approaches have been studied in the neoadjuvant, adjuvant and advanced settings, and there is a wealth of information to guide clinicians managing these patients. Despite this, certain challenges remain.

Areas covered: We reviewed the available literature regarding BRAF mutation types and resistance mechanisms, neoadjuvant and adjuvant approaches for patients with early-stage disease, management of advanced disease, including patients with brain metastases, as well as identified areas of further research.

Expert opinion: Although there is a significant amount of literature to guide the management of BRAF-mutant melanoma, several questions remain. Thus far, the management of stage III BRAF-mutant patients following neoadjuvant ICI, treatment de-escalation in long-term TT responders in the advanced setting and the management of symptomatic brain metastases remain areas of debate. Further work on predictive and prognostic biomarkers for patients with BRAF-mutant melanoma patients will assist in clinical decision-making.

Background: The hemoglobin, albumin, lymphocyte, and platelet (HALP) score could be a prognostic biomarker in patients with cancer as a reflector of nutritional and inflammatory status, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). Therefore, we sought to investigate the relationship between HALP score and survival in ICI-treated patients.

Methods: We included adult patients with advanced cancer treated with ICIs between June 2016 and January 2024. Receiver operating characteristic (ROC) curve analysis was employed to identify the optimal HALP score cutoff point for survival prediction. The Kaplan-Meier method was utilized to create survival curves, and Cox regression was employed for multivariate analysis.

Results: A total of 456 patients were included. The median age was 62 years, and 64.7% were male. The optimal HALP cutoff value for survival prediction was 22.8 in ROC analyses (AUC: 0.624, 95% CI: 0.570-0.679, p < 0.001). Multivariate analysis revealed that patients with low HALP scores had significantly shorter OS (HR: 1.394, 95% CI: 1.077-1.805, p = 0.012) and PFS (HR: 1.388, 95% CI: 1.129-1.706, p = 0.002).

Conclusions: Our study results pointed out the possible use of the HALP score as a prognostic marker in ICI-treated patients. If validated in prospective cohorts, the HALP score could enhance prognosis prediction in ICI-treated patients.

Introduction: Adoptive immunotherapy using chimeric antigen receptor (CAR)-engineered T cells has proven transformative in the management of B cell and plasma cel derived malignancies. However, solid tumors have largely proven to be resistant to this therapeutic modality. Challenges include the paucity of safe target antigens, heterogeneity of target expression within the tumor, difficulty in delivery of CAR T cells to the site of disease, poor penetration within solid tumor deposits and inability to circumvent the array of immunosuppressive and biophysical barriers imposed by the solid tumor microenvironment.

Areas covered: Literature was reviewed on the PubMed database, excluding occasional papers which were not available as open access publications or through other means.

Expert opinion: Here, we have surveyed the large body of technological advances that have been made in the quest to bridge the gap toward successful deployment of CAR T cells for the treatment of solid tumors. These encompass the development of more sophisticated targeting strategies to engage solid tumor cells safely and comprehensively, improved drug delivery solutions, design of novel CAR architectures that achieve improved functional persistence and which resist physical, chemical and biological hurdles present in tumor deposits. Prospects for combination therapies that incorporate CAR T cells are also considered.

Introduction: Resection of primary tumor and liver metastases is the gold standard for colorectal cancer with liver-only metastases (CRLM). Although treatment options have expanded to enable conversion of unresectable to resectable CRLM, about 40% of patients will have definitively unresectable disease. Major advances in surgical techniques, immunosuppressive protocols and patient selection criteria for liver transplantation have resulted in improved outcomes.

Areas covered: A literature search has been conducted in Pubmed for articles published between 2014 and 2024. This review paper comments on current liver-directed treatment options for CRLM: resection, percutaneous ablation, conversion-chemotherapy, TACE, SIRT, and SABR. We explore evidence for liver transplantation in patients with unresectable CRLM, comment on possible limitations for implementation in clinical practice and give an overview of the current guidelines on liver transplantation in the USA, Europe, the United Kingdom, and Australia/New Zealand.

Expert opinion: The recent randomized TRANSMET trial, investigating liver transplantation versus chemotherapy in unresectable CRLM, shows promising 5-year OS reaching similar values as for other accepted liver transplantation indications. Further investigations with RCTs to investigate reproducibility and feasibility in clinical practice are needed. Before liver transplantation can be implemented as a standard treatment option, reorganizations at federal, regional and hospital levels would be required.

Background: Osteosarcoma is a rare and aggressive bone cancer, with targeted therapy using VEGFR-TKIs (Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors) emerging as a promising treatment option.

Research design and methods: This meta-analysis evaluated the efficacy and safety of VEGFR-TKIs in osteosarcoma treatment, analyzing studies from PubMed, Embase, Web of Science, and Cochrane databases until 18 September 2023, involving 14 trials with 447 patients.

Results: Results indicated that monotherapy with VEGFR-TKIs had an objective response rate(ORR) of 16% (95% CI = 9-24%) and a disease control rate(DCR) of 65% (95% CI = 57-73%). The average progression-free survival(PFS) was 4.27 months(95% CI = 3.21-5.34), with overall survival(OS) at 9.26 months(95% CI = 7.75-10.77). Combined treatments led to an ORR of 7% (95% CI = 2-12%) and a DCR of 71% (95% CI = 54-88%), with PFS of 5.62 months(95% CI = 3.57-7.74) and OS of 11.84 months(95% CI = 9.26-14.43). Treatment-related adverse events occurred in 83% (95% CI = 74-92%), with severe events in 32% (95% CI = 3-61%).

Conclusions: In conclusion, VEGFR-TKIs demonstrate effectiveness and tolerability in osteosarcoma treatment, providing significant disease control and survival advantages despite notable adverse event risks.

Registration: PROSPERO (CRD42024579648).

Introduction: Platinum rechallenge is recommended for patients with small cell lung cancer (SCLC) who relapse ≥90 days after completing first-line chemotherapy, although it may not always be the most suitable option.

Areas covered: Articles for review were identified via PubMed and ClinicalTrials.gov searches, supplemented with non-indexed publications (e.g. conference abstracts) known to the manufacturer. We examined evidence for platinum re-exposure in patients with sensitive relapsed SCLC, and present lurbinectedin as a potential alternative. The complementary mechanisms of action of lurbinectedin and platinum, owing to opposite sensitivity of SCLC cells, may resensitize tumor cells to platinum. As efficacy outcomes with lurbinectedin are equivalent or better than those with platinum rechallenge and its hematological safety profile is more favorable, achieving maximum dose intensity is more likely. The simpler dosing schedule of lurbinectedin (1 vs 3 days) and lack of need for granulocyte colony-stimulating factor primary prophylaxis lessens treatment burden.

Expert opinion: Incorporation of lurbinectedin into therapeutic algorithms for relapsed SCLC has challenged long-established treatment paradigms. Initial evidence indicates that using lurbinectedin after failure of first-line platinum may prolong the platinum-free interval and reserve platinum for later use. Current evidence supports lurbinectedin as a second-line option in patients with sensitive relapsed SCLC.