Expert Review of Anticancer Therapy最新文献

Introduction: A tyrosine-kinase inhibitor (TKI) is indicated as a first-line treatment for patients with non-small-cell lung cancer (NSCLC) harboring an epidermal growth-factor - receptor (EGFR) mutation. Chemotherapy (ChT) given in combination with an EGFR-TKI in this setting is of interest.

Methods: We conducted a meta-analysis of phase III randomized trials comparing EGFR-TKI + ChT vs. EGFR-TKI alone as first-line therapy for advanced NSCLC harboring an activating EGFR mutation.

Results: Three studies evaluated gefitinib + ChT (NEJ009, GAP-Brain, and Noronha et al.) and another evaluated osimertinib + ChT (FLAURA-2). Those four eligible studies included 1413 patients with non-squamous NSCLCs, 826 (58%) with an exon-19 deletion (ex19del) and 541 (38%) with EGFR^L858R. The EGFR-TKI + ChT combination was significantly associated with prolonged PFS (hazard ratio [HR]: 0.52 [95% confidence interval (CI): 0.45-0.59]; p < 0.0001) and OS (HR: 0.69 [0.52-0.93]; p = 0.01). PFS was particularly improved for patients with brain metastases (HR: 0.41[0.33-0.51]; p < 0.00001).

Conclusions: For patients with untreated, advanced, EGFR-mutated NSCLCs, the EGFR-TKI + ChT combination, compared to EGFR-TKI alone, was associated with significantly prolonged PFS and OS. However, further studies are needed to identify which patients will benefit the most from the combination.

Registration: PROSPERO CRD42024508055.

Objectives: This study aimed to explore the factors affecting the overall survival (OS) of giant hepatocellular carcinoma (G-HCC) patients and establish a nomogram and an Internet-based OS calculator for evaluating the OS of G-HCC patients.

Research design and methods: A total of 2445 G-HCC patients were searched in the SEER database. The independent variables affecting OS of G-HCC patients were determined by univariate and multivariate analyses, and a nomogram and Internet-based OS calculator were established. The accuracy of the nomogram was evaluated by the C-index, the AUC curve, and calibration curve.

Results: Grade, surgery, radiotherapy, chemotherapy, T-staging, M-staging, AFP, and fibrosis were identified as independent variables affecting OS. These variables were included in the nomogram model and Internet-based OS calculator to evaluate OS in G-HCC patients. The C-indices and AUC of the nomogram are better than AJCC-staging system. Similarly, the calibration curves revealed that the actual survival was consistent with nomogram-based survival.

Conclusion: The nomogram and Internet-based OS calculator are superior to the traditional AJCC-staging system in the reliability and convenience of prognosis assessment for G-HCC patients, which is more conducive for clinicians to predict the survival of G-HCC patients and make the best treatment strategy.

Introduction: The management of relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) has witnessed dramatic changes in the recent past. Despite the availability of multiple novel immunotherapies in R/R setting, there remains an unmet need for off-the-shelf therapies, particularly in patients with primary refractory, multiply relapsed disease or those experiencing cellular immunotherapy failure. To harness the power of the T-cell mediated immunity, a novel class of drugs called bispecific antibodies (BsAbs) have been developed. These BsAbs are currently under investigation both in frontline and R/R setting and hold the potential to revolutionize the management of LBCL.

Areas covered: This review article summarizes the currently available BsAbs, their mode of action, efficacy, and safety data for untreated and R/R LBCL. In addition, the role of these BsAbs in combination with currently available chemoimmunotherapy regimens is also discussed.

Expert opinion: Two BsAbs have secured FDA approval for R/R LBCL, with expected approval of more BsAbs (including in earlier treatment lines). These drugs provide a highly efficacious and relatively safe treatment option for patients with highly pretreated disease including relapse after cellular immunotherapies. In addition, these BsAbs provide a platform for chemotherapy-free regimen for older/frail patients.

Introduction: Systemic and local therapies for patients with metastatic renal cell carcinoma (mRCC) are often challenging despite the evolution of multimodal cancer therapies in the last decade. In this review, we will focus on recent multidisciplinary approaches for patients with mRCC.

Areas covered: Systemic therapies for patients with mRCC have been garnering attention particularly after the approval of immuno-oncology (IO) agents, including anti-programmed death 1/programmed death-ligand 1. IO combinations have significantly prolonged overall survival in patients with mRCC in the first-line setting. Regarding local therapies, cytoreductive nephrectomy (CN) has become less common in the post-Cancer du Rein Metastatique Nephrectomie et Antiangiogéniques (CARMENA) trial era, even though CN may still benefit selected patients with mRCC. In addition, metastasis-directed local therapies, namely metastasectomy or stereotactic radiotherapy, particularly for oligo-metastatic lesions or brain metastases, may have a prognostic impact. Several ablative techniques are also evolving while maintaining high local control rates with acceptable safety.

Expert opinion: Multimodal cancer therapies are essential for conquering complex cases of mRCC. Modern systemic therapies including IO-based combination therapy as well as local therapies including CN, metastasectomy, stereotactic radiotherapy, and ablative techniques appear to improve oncologic outcomes of patients with mRCC, although appropriate patient selection is indispensable.

Introduction: Uterine cancer is the most common gynecologic malignancy in women and is projected to surpass ovarian cancer as the deadliest gynecologic malignancy in the United States in 2024. Additionally, rates of advanced and high-risk uterine cancer have been on the rise in the United States, demonstrating a need for innovation in treatment options. There have been multiple recent trials investigating the incorporation of novel agents in the treatment of advanced and recurrent endometrial cancer.

Areas covered: This article will discuss the current landscape of the treatment of advanced and recurrent endometrial cancer, focusing on recent phase III trials published or presented on with the incorporation of immunotherapy and other novel therapeutics while also reviewing promising phase I and II trials in the field. Clinical trials were identified via clinicaltrials.gov and a PubMed literature search was performed (initially February 2024, updated May 2024).

Expert opinion: The treatment field is promising for patients as many of these trials appear to offer progression free and overall survival benefits in a disease with a historically poor prognosis. Molecular profiling of endometrial cancer will be the backbone of treatment paradigms in the future.

Introduction: Climate change and global warming are an omnipresent topic in our daily lives. Planetary health and oncology represent two critical domains within the broader spectrum of healthcare, each addressing distinct yet interconnected aspects of human well-being. We are encouraged to do our part in saving our planet. This should include the decisions we make in our professional life, especially in uro-oncology, as the healthcare sector significantly contributes to environmental pollution.

Areas covered: There are many aspects that can be addressed in the healthcare sector in general, as there are structural problems in terms of energy consumption, water waste, therapeutic techniques, transportation and drug manufacturing, as well as in uro-oncology specific areas. For example, the use of different surgical techniques, forms of anesthesia and the use of disposable or reusable instruments, each has a different impact on our environment. The literature search was carried out using PubMed, a medical database.

Expert opinion: We are used to making decisions based on the best outcome for patients without considering the impact that each decision can have on the environment. In the present article, we outline options and choices for a more climate-friendly approach in urologic oncology.

Introduction: Advances in molecular biology have led to consensus classification of medulloblastoma into four broad molecular subgroups - wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4, respectively. Traditionally, children >3 years of age, with no/minimal residual tumor (<1.5 cm²) and lack of metastasis were classified as average-risk disease with >80% long-term survival. Younger age (<3 years), large residual disease (≥1.5 cm²), and leptomeningeal metastases either alone or in combination were considered high-risk features yielding much worse 5-year survival (30-60%). This clinico-radiological risk-stratification has been refined by incorporating molecular/genetic information. Contemporary multi-modality management for non-infantile medulloblastoma entails maximal safe resection followed by risk-stratified adjuvant radio(chemo)therapy. Aggressive multi-modality management achieves good survival but is associated with substantial dose-dependent treatment-related toxicity prompting conduct of subgroup-specific prospective clinical trials.

Areas covered: We conducted literature search on PubMed from 1969 till 2023 to identify putative prognostic factors and risk-stratification for medulloblastoma, including molecular subgrouping. Based on previously published data, including our own institutional experience, we discuss molecular risk-stratification focusing on WNT-pathway medulloblastoma to identify candidates suitable for treatment de-intensification to strike the optimal balance between survival and quality of survivorship.

Expert opinion: Prospective clinical trials and emerging biological information should further refine risk-stratification in WNT-pathway medulloblastoma.

Introduction: Adenoid cystic carcinoma of minor salivary glands (AdCCmSG) represents a 'rarity in the rarity,' posing a clinical challenge in lack of standardized, evidence-based recommendations. At present, AdCCmSG management is mostly translated from major salivary gland cancers (MSGCs). Ideally, AdCCmSG diagnostic-therapeutic workup should be discussed and carried out within a multidisciplinary, high-expertise setting, including pathologists, surgeons, radiation oncologists and medical oncologists.

Areas covered: The present review provides an overview of epidemiology and pathologic classification. Moreover, the most recent, clinically relevant updates in the treatment of AdCCmSG (Pubmed searches, specific guidelines) are critically discussed, aiming to a better understanding of this rare pathologic entity, potentially optimizing the care process, and offering a starting point for reflection on future therapeutic developments.

Expert opinion: The management of rare cancers is often hindered by limited data and clinical trials, lack of evidence-based guidelines, and hardly represented disease heterogeneity, which cannot be successfully tackled with a 'one-size-fits-all' approach. Our goal is to address these potential pitfalls, providing an easy-to-use, updated, multidisciplinary collection of expert opinions concerning AdCCmSG management as of today's clinical practice. We will also cover the most promising future perspectives, based on the potential therapeutic targets highlighted within AdCCmSG's molecular background.