Future oncology最新文献

Aim: Describe real-world epidemiology, treatment patterns, health care resource utilization, and costs of locally advanced or metastatic urothelial carcinoma (la/mUC) in France.

Patients & methods: Retrospective study including all adults with la/mUC diagnosis during January 2017 to December 2020 in the PMSI database.

Results: Annual prevalence and incidence ranged from 36.4 to 38.9 and 16.4 to 18.5 cases per 100,000 people, respectively. Of the 25,314 patients with incident la/mUC, 37.6% did not receive first-line systemic treatment. Of the 14,656 patients who started first-line systemic treatment, 66.6%, 22.5%, and 10.9% received 1, 2, and 3 lines of therapy, respectively. Annual per-patient costs in second-/third-line setting ranged from €8803 to €16,012.

Conclusion: The substantial disease burden of la/mUC in France highlights the unmet need for new therapies.

Introduction: To quantify physicians' preferences for adjuvant renal cell carcinoma (RCC) treatments.

Materials and methods: A discrete-choice experiment was administered online to board-certified/eligible physicians. Physicians chose between pairs of hypothetical adjuvant therapies for a high-risk patient who had recently undergone a radical nephrectomy. Data were analyzed using random-parameters logit and latent-class models.

Results: Physicians (n = 250; 64% oncologists; 36% urologists) placed most importance on improvements in the chance of 5-year overall survival, followed by increased median disease-free survival and reduced risk of side effects. The analyses also highlighted their willingness to make tradeoffs between these benefits and risks. Physicians were generally tolerant of increases in the risks of treatment-related severe diarrhea, dizziness, and fatigue and were willing to accept increases in these risks in exchange for improvements in overall or disease-free survival. Subgroup analysis revealed heterogeneity between oncologists and urologists, and latent-class analysis revealed significant heterogeneity among the whole physician sample.

Conclusions: Most physicians in this study would recommend adjuvant therapy to a typical high-risk postnephrectomy RCC patient.

Triple-negative breast cancer (TNBC) presents a formidable global health challenge, marked by its aggressive behavior and significant treatment resistance. This subtype, devoid of estrogen, progesterone, and HER2 receptors, largely relies on breast cancer stem cells (BCSCs) for its progression, metastasis, and recurrence. BCSCs, characterized by their self-renewal capacity and resistance to conventional therapies, exploit key surface markers and critical signaling pathways like Wnt, Hedgehog, Notch, TGF-β, PI3K/AKT/mTOR and Hippo-YAP/TAZ to thrive. Their adaptability is underscored by mechanisms including drug efflux and enhanced DNA repair, contributing to poor prognosis and high recurrence rates. The tumor microenvironment (TME) further facilitates BCSC survival through complex interactions with stromal and immune cells. Emerging therapeutic strategies targeting BCSCs - ranging from immunotherapy and nanoparticle-based drug delivery systems to gene-editing technologies - aim to disrupt these resistant cells. Additionally, innovative approaches focusing on exosome-mediated signaling and metabolic reprogramming show promise in overcoming chemoresistance. By elucidating the distinct characteristics of BCSCs and their role in TNBC, researchers are paving the way for novel treatments that may effectively eradicate these resilient cells, mitigate metastasis, and ultimately improve patient outcomes. This review highlights the urgent need for targeted strategies that address the unique biology of BCSCs in the pursuit of more effective therapeutic interventions for TNBC.

In the evolving therapeutic landscape of chronic myeloid leukemia (CML), asciminib stands out as a critical treatment option. Its ability to bind to and allosterically modulate the myristoyl pocket of BCR::ABL1 enables asciminib to effectively overcome resistance to conventional tyrosine kinase inhibitors (TKIs). Asciminib has shown significant cytogenetic and molecular responses in heavily pretreated patients, those previously exposed to ponatinib, and treatment-naïve individuals, attributed to its pharmacological selectivity and generally favorable safety profile. Asciminib also offers a compelling alternative for patients with a history of cardiovascular events or unfavorable cardiovascular profiles. However, extended follow-up in ongoing trials is necessary for a thorough assessment of its long-term benefits. Mutations in the myristoyl pocket, such as A337V/T and I502L, along with kinase domain mutations, including F359C/I/V at the kinase-SH2 interface and M244V in the N-lobe, have demonstrated the ability to undermine asciminib effectiveness in clinical practice, highlighting the importance of mutational assessment before starting treatment. This review provides an in-depth analysis of the preclinical and clinical evidence supporting the use of asciminib, synthesizing findings from a targeted literature search of PubMed and Web of Science. Our discussion integrates insights into its mechanism of action, clinical efficacy, safety, resistance patterns, and future directions.

Introduction: To quantify patients' preferences for adjuvant renal cell carcinoma (RCC) treatments.

Patients and methods: Preferences were elicited using a discrete-choice experiment requiring RCC patients to choose between 2 hypothetical treatments. Data were analyzed using random-parameters logit and latent-class models.

Results: Patients (n = 250) preferred treatments that increase disease-free and overall survival (OS), are taken less frequently, require no concomitant medication, have a shorter duration, and have lower side-effect risks. The analyses also highlighted their willingness to make tradeoffs between these benefits and risks. Patients were generally tolerant of increases in the risks of treatment-related severe diarrhea, dizziness, and fatigue and were willing to accept increases in these risks in exchange for improvements in overall or disease-free survival. Latent-class analysis identified 3 classes: class 1 (37.5%) and class 2 (26.9%) preferred not to opt out of treatment and prioritized increased OS and disease-free survival, respectively; class 3 (35.5%) preferred to opt out and prioritized mode, duration, and risks.

Conclusions: Heterogeneity suggests patient-physician discussions are important when considering RCC treatments.

Previous phase I/II trials indicate promising activity of lurbinectedin plus doxorubicin (DOX) in leiomyosarcoma (LMS). We describe here the rationale and design of SaLuDo, an open label, randomized, multicenter, seamless phase IIb/III study to evaluate the antitumor activity and safety of lurbinectedin plus DOX versus DOX alone in the first-line setting of metastatic LMS. The phase IIb stage will evaluate two schedules of the combination for the phase III stage given every 3 weeks (q3wk): DOX 50 mg/m² plus lurbinectedin 2.2 mg/m², and DOX 25 mg/m² plus lurbinectedin 3.2 mg/m². The control arm will be DOX 75 mg/m² q3wk. The primary endpoint is progression-free survival by independent review; overall survival is the key secondary endpoint. Clinical trial registration: www.clinicaltrials.gov identifier is NCT06088290.

Introduction: FOLFIRINOX, a primary chemotherapy for metastatic pancreatic cancer, often causes severe toxicity, necessitating hospitalization and dose adjustments. This study aims to identify predictors of FOLFIRINOX toxicity, focusing on biological, clinical, and anthropometric factors.

Material & methods: This retrospective study analyzes pancreatic adenocarcinoma patients on FOLFIRINOX, assessing pre-treatment biological, clinical, and anthropometric traits. Hospitalizations and tolerance during the first chemotherapy month were evaluated using CTCAE v5.0 grading, with early toxicity assessed via anthropometric factors using Anthropometer3DNet software from pre-treatment scans.

Results: In 152 pancreatic cancer patients (median age: 62), FOLFIRINOX was administered in metastatic (81%), locally advanced (14%), and adjuvant/neoadjuvant (5%) settings. Performance Status was zero (49%), one (41%) and ≥ 2 (10%). Median follow-up was 62.5 months, with median overall survival of 13.7 months and progression-free survival of 8.9 months. First-cycle dose reduction occurred in 14% of patients. Within the first month, 48% experienced toxicity leading to hospitalization and/or dose reduction, with 28% requiring a median 8-day hospitalization. Low muscle body mass (MBM) significantly correlated with dose reduction (AUC 0.63; p = 0.005). An NLR ratio less than 4 was significantly associated with longer OS (p = 0.001).

Conclusion: Low MBM is linked to FOLFIRINOX toxicity, suggesting MBM assessment could allow better selection of patients to avoid these toxicities, warranting further confirmation in larger cohorts.

Selinexor is an investigational, selective oral XPO1 inhibitor that may inhibit myelofibrosis (MF)-relevant JAK/STAT and non-JAK/STAT pathways with potential synergy with ruxolitinib. SENTRY (XPORT-MF-034; NCT04562389) is a Phase 1/3 study evaluating safety and efficacy of selinexor plus ruxolitinib for treatment of patients with JAK inhibitor (JAKi) treatment-naïve MF. The Phase 1 open label portion of the study included a 3 + 3 dose escalation and dose expansion, with no dose limiting toxicities observed. Described here is the Phase 3 randomized, double-blind, placebo-controlled study designed to evaluate selinexor+ruxolitinib versus placebo+ruxolitinib in patients with JAKi treatment-naïve MF. Approximately 350 patients will be enrolled. Primary endpoints will evaluate spleen volume reduction ≥ 35% and absolute mean change in total symptom score from baseline to week 24.Clinical Trial Registration: NCT04562389 (ClinicalTrials.Gov).