Cancer treatment reviews最新文献

Introduction: Antibody-drug conjugates (ADCs) trastuzumab-deruxtecan (T-DXd) and sacituzumab-govitecan (SG) provided significant progression-free survival (PFS) and overall survival (OS) improvements over chemotherapy (CT) in pretreated hormone receptor-positive (HR+) and triple-negative (TN)/HER2-low metastatic breast cancer (MBC). However, no direct comparison between the two exists, nor with the more recent datopotamab-deruxtecan (Dato-DXd).

Methods: We conducted a network meta-analysis (NMA) to compare efficacy and safety of T-DXd and SG in CT-pretreated HR+ and TN/HER2-low MBC and assess their benefit over standard CT, exploring also a comparison with Dato-DXd. Hazard ratios (HRs) with 95 % confidence intervals (CI) were calculated for PFS/OS. P-score was used for treatment ranking.

Results: Three RCTs (956 patients) were included in the primary analysis and 5 (1,445) in the exploratory NMA with Dato-DXd. In HR+/HER2-low, T-DXd showed no significant difference in PFS and OS when compared to SG. Similarly, in TN/HER2-low, PFS and OS did not differ significantly between the two ADCs. The P-score analysis favored T-DXd over SG in HR+/HER2-low in PFS (0.90 vs. 0.60) and OS (0.89 vs. 0.60). SG was favored over T-DXd in OS in TN/HER2-low (0.80 vs. 0.69). Similar results were obtained for HR+ MBC when including Dato-Dxd, which showed the worst performance, while T-DXd was the only ADC significantly outperforming CT in OS. The ADCs showed significantly better PFS and OS than CT in HR+/HER2-low and TN/HER2-low (all p < 0.001). SG had higher rates of neutropenia, diarrhea and alopecia vs. T-DXd, which showed more thrombocytopenia, fatigue and nausea. Pneumonitis and cardiotoxicity were typically T-DXd-related, and T-DXd showed more toxicity-related discontinuations.

Conclusions: Similar efficacy with T-DXd and SG in HER2-low MBC was observed, regardless of HR status. Safety profile, local drug-approval criteria and guidelines, patients' preferences and overall quality of evidence should ultimately guide therapeutic decision-making. Dato-DXd role remains uncertain.

Head and neck squamous cell carcinoma (HNSCC) is a malignancy with a poor prognosis, and the majority of patients with HNSCC are diagnosed at later stages owing to its hidden anatomical location and atypical clinical symptoms. It is notably prone to recurrence and metastasis. The traditional treatments include surgery, radiotherapy, chemotherapy, and targeted therapy. Although multiple treatment strategies have been established, the prognosis remains poor because most patients develop resistance to traditional treatments. In recent years, epidermal growth factor receptor (EGFR) inhibitors and immune checkpoint inhibitors (ICIs) have been shown to provide clinical benefits to these patients. Based on the promising results of both anti-EGFR therapy and immunotherapy, as well as the biological rationale for combining immunotherapy with anti-EGFR drugs, numerous preclinical and ongoing or completed clinical trials have explored the use of their synergistic effects. This review summarizes the feasibility of combining immunotherapy with EGFR inhibitors for HNSCC treatment and analyses the relevant biomarkers. It also summarizes the strategies for clinical applications. We found that immunotherapy and EGFR inhibitor combination therapy showed promise in treating patients with HNSCC and exhibited safety with acceptable adverse events. This review may provide valuable insights for the future development of treatments and formulation of therapeutic strategies for HNSCC, as well as useful information for the future design of clinical trials.

Dysregulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway plays a pivotal role in the development and progression of various cancers. In hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer, aberrations in this pathway are increasingly recognized as key drivers of resistance to endocrine therapy and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, the first-line treatments for this disease subtype. Recognizing the urgent need for alternative therapeutic strategies, significant advancements have been made in developing PI3K/AKT/mTOR inhibitors for HR+ advanced/metastatic breast cancer. Among these inhibitors, capivasertib and alpelisib have received approval as targeted therapies for this indication. This review provides a comprehensive summary of the latest developments in PI3K/AKT/mTOR inhibitors for HR+ breast cancer. It also delves into different aspects, including sampling, testing method and timing, of PI3K/AKT/mTOR diagnostic testing. Additionally, the review discusses key considerations for integrating these inhibitors into clinical practice, such as timing and choice of PI3K/AKT/mTOR inhibitors, and management of treatment toxicities. By examining these different aspects, this review aims to provide valuable insights into optimizing the clinical utility of PI3K/AKT/mTOR inhibitors in HR+ advanced breast cancer.

Background: Local resection (LR) methods for rectal cancer are generally considered in the palliative setting or for patients deemed a high anaesthetic risk. This systematic review and meta-analysis aimed to compare oncological outcomes of LR and radical resection (RR) for early rectal cancer in the context of staging and surveillance assessment.

Methods: A literature search of MEDLINE, Embase and Emcare databases was performed for studies that reported data on clinical outcomes for both LR and RR for early rectal cancer from January 1995 to April 2023. Meta-analysis was performed using random-effect models and between-study heterogeneity was assessed. The quality of assessment was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias 2.0 tool for randomised controlled trials.

Results: Twenty studies with 12,022 patients were included: 6,476 patients had LR and 5,546 patients underwent RR. RR led to an improvement in 5-year overall survival (OR 1.84; 95 % CI 1.54-2.20; p < 0.0001; I² 20 %) and local recurrence (OR 3.06; 95 % CI 2.02-4.64; p < 0.0001; I² 39 %) when compared to LR. However, when staging and surveillance methods were clearly adopted in LR cases, there was an improvement in R0 rates (96.7 % vs 85.6 %), 5-year disease-free survival (93.0 % vs 77.9 %) and overall survival (81.6 % vs 79.0 %) compared to when staging and surveillance was not reported/performed.

Conclusions: LR may be appropriate for selected patients without poor prognostic factors in early rectal cancer. This study also highlights that there is currently no single standardised staging or surveillance approach being adopted in the management of early rectal cancer. A more specified and standardised preoperative staging for patient selection as well as clinical and image-based surveillance protocols is needed.