Future oncology最新文献

Aims: Limited head-to-head data exist for daratumumab plus pomalidomide and dexamethasone (DPd) and non-pomalidomide-containing triplet regimens to treat relapsed/refractory multiple myeloma (RRMM). This study conducted population-adjusted indirect comparisons of overall survival (OS) for DPd vs. daratumumab, carfilzomib, and dexamethasone (DKd) and daratumumab, bortezomib, and dexamethasone (DVd).

Materials & methods: A systematic literature review was performed via searches of databases and relevant conference proceedings. Both simulated treatment comparison (STC) and matching-adjusted indirect comparison (MAIC) were used to adjust for between-trial differences.

Results: Seven randomized controlled trials were identified, five of which were subsequently excluded from the indirect treatment comparison during feasibility assessment. A consistent OS benefit was observed for DPd vs. DKd and DVd for patients with RRMM, using both STC and MAIC methods.

Conclusions: The findings of this study support the use of DPd over DKd and DVd for the treatment of patients with early RRMM.

Metastatic prostate cancer remains incurable. Though significant progress has been made in the field, the search for agents that improve outcomes for patients is ongoing. Several clinical trials have explored the benefit of combining PARP inhibitors (PARPi) with androgen receptor pathway inhibitors (ARPIs) for metastatic castrate resistant prostate cancer (mCRPC), especially those cancers with alterations in homologous recombination repair (HRR) genes. Niraparib, a highly selective inhibitor of PARP1 and PARP2, has been shown to confer a radiographic progression-free survival benefit in the treatment of mCRPC with HRR-associated gene alterations, particularly BRCA1 and BRCA2 (BRCA1/2), when combined with abiraterone acetate plus prednisolone (AAP). This combination has recently been approved in the USA, Canada and Europe for patients with mCRPC and a BRCA1/2 gene mutation. This review summarizes the evidence with regards to the pharmacologic activity and clinical efficacy of niraparib with a specific focus on its efficacy in combination with AAP in mCRPC patients with HRR alterations.

Aim: Cancers lacking standard screening (LSS) options account for approximately 70% of cancer-related deaths due to late-stage diagnosis. Circulating tumor DNA (ctDNA) is a promising biomarker for multi-cancer early detection. We previously developed SPOT-MAS, a multimodal ctDNA-based assay analyzing methylation and fragmentomic profiles, effective in detecting common cancers (breast, colorectal, liver, lung and gastric). This study extends the analysis to five LSS cancers: endometrial, esophageal, head and neck, ovarian and pancreatic.Methods: SPOT-MAS was applied to profile cfDNA methylation and fragmentomic patterns in 739 healthy individuals and 135 LSS cancer patients.Results: We identified 347 differentially methylated regions and observed genome-wide hypomethylation across all five LSS cancers. Esophageal and head and neck cancers showed an enrichment of short cfDNA fragments (<150 bp). Eleven 4-mer end motifs were consistently altered in cfDNA fragments across all LSS cancers. Many significant signatures were consistent with previous observations in common cancers. Notably, SPOT-MAS achieved 96.2% specificity and 74.8% overall sensitivity, with a lower sensitivity of 60.7% in early-stage cancers.Conclusion: This proof-of-concept study demonstrates that SPOT-MAS a non-invasive test trained on five common cancer types, could detect a number of LSS cancer cases, potentially complementing existing screening programs.

What is this summary about?: This summary includes information from the ARCHES and ENZAMET follow-up studies. Both studies looked at enzalutamide treatment for people with metastatic hormone-sensitive prostate cancer (known as mHSPC). In ARCHES, researchers compared the medications enzalutamide + androgen deprivation therapy (known as ADT) with placebo + ADT. In ENZAMET, researchers compared enzalutamide + ADT with standard treatment + ADT. Some people in ENZAMET also took enzalutamide with docetaxel (a chemotherapy treatment). In both studies, researchers wanted to find out if enzalutamide helps people with mHSPC live longer.

What are the key takeaways?: In both studies, researchers found that people with mHSPC who took enzalutamide lived longer than people who did not. People who took enzalutamide also lived longer without their cancer getting worse. The results were mostly similar in groups of people dependingon when and where their cancer was found. Researchers did not find any new safety concerns.

What were the main conclusions?: People with mHSPC may benefit from long-term treatment with enzalutamide + ADT. They may also benefit from taking enzalutamide with other treatments, like docetaxel. It may be better for people with mHSPC to have enzalutamide treatment before their cancer gets worse, rather than waiting. These people and their doctors should carefully consider the benefits and risks of each treatment to make a joint decision for treating mHSPC.Clinical Trial Registration: NCT02677896 (ARCHES), NCT02446405 (ENZAMET) (ClinicalTrials.gov).

Patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) have very poor long-term outcomes. Allogeneic stem cell transplantation (allo-SCT) can potentially cure some of these patients who are able to achieve a second or greater remission with salvage chemotherapy. Unfortunately, several barriers exist to transplantation and not all patients with r/r AML are able to proceed to allo-SCT. Therefore, novel therapies to decrease the risk of relapse in these patients are urgently needed. Wilms tumor 1 (WT1) protein has emerged as an encouraging vaccine target in AML due to its overexpression in leukemic blast cells and near absence in normal hematopoietic cells. Maintenance therapy with galinpepimut-S, a multivalent heteroclitic WT1 peptide vaccine, holds promise in early phase trials, in patients with AML by inducing a strong innate immune response against the WT1 antigen, leading to the design of this international, open-label, randomized clinical trial, named REGAL. Clinical trial registration: https://clinicaltrials.gov/study/NCT04229979. The clinical trial identifier is NCT04229979.

People living with cancer should have access to clear and comprehensible treatment information to empower informed decision-making. With the increasing adoption of open access publishing and plain-language summaries, clinical trial findings in journals are becoming more accessible. However, this will only help patients if they are equipped with the relevant knowledge and understanding to make sense of these findings. This podcast highlights the need to support this aspect of health literacy by bringing together the perspectives of a patient, a patient advocate and a medical oncologist. It is accompanied by two visual, plain-language guides designed to help general audiences understand the key efficacy end points that are commonly used in trials of solid tumor treatments.

Esophageal squamous cell carcinoma (ESCC) is a severe malignant tumor of the digestive system that poses a significant threat to human health. Despite its significance, the complex molecular mechanism regulating the occurrence and development of ESCC remain elusive. The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) members constitute a pivotal subfamily of the APOBEC family that possess cytidine deaminase activity. In recent years, APOBEC3s (A3s) have received increasing attention due to their pivotal roles in the occurrence, development, and prognosis of ESCC. This comprehensive review systematically summarizes the latest research progress on the mechanisms of action of A3s in ESCC and discusses their impact on the development and therapeutic considerations for ESCC, with a particular focus on their potential role in immunotherapy. These insights may be of great value in continued exploration of ESCC pathogenesis and provides a theoretical foundation for the development of clinical treatment strategies for ESCC.

Treatment of non-small-cell lung cancers (NSCLC) has evolved over the last decade. According to studies, the use of targeted therapies has significantly increased the life expectancy of patients. Moreover, ALK-tyrosine kinase inhibitors (ALK-TKIs) have improved clinical outcomes. In Lebanon, translating recommendations into clinical practice remains challenging. A Lebanese expert panel of oncologists was convened to describe the management paradigm and the clinical evidence supporting the optimal use of next-generation TKIs in patients with ALK-rearranged NSCLC and to provide an expert overview of local challenges and recommendations for optimizing the management of advanced NSCLC in Lebanese patients. The experts agreed that these recommendations should be part of a healthcare strategy to be implemented at the national level.

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