Future oncology最新文献

The BREAKWATER Phase III study investigated encorafenib and cetuximab plus mFOLFOX6 versus chemotherapy with or without bevacizumab for the treatment of patients with previously untreated BRAF V600E - mutant metastatic colorectal cancer. The study showed significantly improved objective response rate by blinded independent central review, and significantly longer progression-free survival by blinded independent central review and overall survival in patients treated with first-line encorafenib and cetuximab plus mFOLFOX6 compared with chemotherapy with or without bevacizumab. The safety profiles were consistent with those known for each agent. These results led to the approval of encorafenib and cetuximab plus mFOLFOX6 for the treatment of BRAF V600E-mutant metastatic colorectal cancer, including in the first line. This paradigm shift in metastatic colorectal cancer highlights the importance for early genomic testing to identify patients who would benefit from this new treatment option. We discuss the results from BREAKWATER - including progression-free survival by blinded independent central review, overall survival, objective response rate by blinded independent central review in all participants, and safety - and the meaning of these results for clinical practice as a new treatment option and the need for earlier genomic testing.Clinical Trial Registration: www.clinicaltrials.gov identifier is NCT04607421.

Background: Although immune checkpoint inhibitors (ICIs) form the cornerstone of first-line treatment for non-small cell lung cancer (NSCLC), the challenge remains to improve patients' long-term outcomes. Eftilagimod alfa (efti) activates antigen-presenting cells, triggering T cell activation and a sustained immune response. Prior studies combining efti with an ICI, pembrolizumab, have shown encouraging efficacy, especially in PD-L1 low (tumor proportion score [TPS] 1-49%) and negative (<1%) tumors. TACTI-004 is a global double-blinded, randomized, placebo-controlled phase III study investigating efti plus standard-of-care (SoC: pembrolizumab plus chemotherapy) in first-line NSCLC, regardless of PD-L1 expression (TPS 0-100%).

Patients and methods: About 756 participants with squamous or non-squamous first-line NSCLC, not amenable to EGFR/ROS1/ALK-targeted therapy, will be randomized to receive either efti plus SoC or placebo plus SoC. The dual primary endpoint is progression-free survival and overall survival. Key secondary endpoints include objective response rate, duration of response and safety. Participants will receive 30 mg efti subcutaneously every 2 weeks (q2w) for 24 weeks, then q3w and pembrolizumab 200 mg intravenously q3w, both for up to 2 years. Chemotherapy choice will be histology-dependent.

Conclusions: TACTI-004 will evaluate whether efti can mitigate resistance to ICIs when added to SoC in NSCLC, irrespective of PD-L1 tumor status.

Clinical trial registration: www.clinicaltrials.gov identifier is NCT06726265.

Introduction: This systematic review and meta-analysis compared the diagnostic performance and complication profiles of transperineal biopsy (TPBx) versus transrectal biopsy (TRBx) for prostate cancer, incorporating recent randomized and large observational studies.

Methods: Following PRISMA 2020 guidelines, PubMed, Scopus, Embase, and Cochrane Library were searched till April 2025. Studies directly comparing TPBx and TRBx were included. Risk of bias was assessed using RoB 2.0 for randomized trials and the Newcastle - Ottawa Scale for observational studies. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models. Subgroup analyses and a GRADE assessment were performed to evaluate the certainty of evidence.

Results: Twenty-nine studies (n = 90,621) were included. TPBx showed higher PCa detection (RR 1.08; 95% CI 1.01-1.15; p = 0.02) and csPCa detection (RR 1.14; 95% CI 1.05-1.24; p = 0.001), though the certainty of evidence was low to moderate. Heterogeneity was moderate to high. TPBx also showed lower infection-related complications and comparable overall events, though procedure-related pain was slightly higher.

Conclusion: TPBx offers improved diagnostic yield and lower infection risk compared with TRBx, with comparable safety. However, given the moderate heterogeneity and limited high-quality RCTs, further confirmatory trials are necessary.

Protocol registration: https://www.crd.york.ac.uk/PROSPERO identifier is CRD420251035763.

Aims: Notable sex-based disparities exist in papillary thyroid carcinoma (PTC), necessitating male-specific models for predicting lateral lymph node metastasis (LLNM) to guide treatment.

Methods: We developed and validated two nomograms, based on central lymph node ratio (LNR) and preoperative ultrasound (US), respectively, using data from 433 male PTC patients who underwent total thyroidectomy (TT) with central and lateral neck lymph node dissection. Multivariable analysis identified key risk factors. Model performance was evaluated using ROC curves, calibration curves, and decision curve analysis (DCA) across training and validation sets.

Results: Male patients had 1.33-fold higher odds of central lymph node metastasis (CLNM) and 1.51-fold higher odds of LLNM than female patients (p < 0.05). Multivariable analysis identified multifocality, tumor size >20 mm, preoperative US nodal status, and an elevated LNR as independent risk factors for LLNM in males (p < 0.05). The LNR-based nomogram demonstrated superior predictive accuracy, with AUCs of 0.828 (training), 0.812 (internal validation), and 0.832 (external validation), outperforming the US-based model. Risk stratification using nomogram scores effectively categorized patients into three distinct groups with significantly different LLNM rates.

Conclusions: The nomogram based on the central LNR provides a precise and clinically valuable tool for the individualized prediction of LLNM in male PTC patients.

Objective: Tradeoffs between efficacy, safety, and administration may influence decision-making for first-line (1L) treatments for ALK+ mNSCLC. This study explored heterogeneity in provider preferences.

Methods: A survey of US oncologists treating ≥1 ALK+ mNSCLC patient was conducted June-August 2024. Participants answered 12 questions comparing 1 L profiles characterized by eight treatment attributes for patients without brain metastases. Attributes included 3-year PFS, intracranial duration of response (iDOR), 16-month risk of edema, myalgia, or cognitive effects, grade ≥3 interstitial lung disease/pneumonitis, 2 L+ treatment options, and administration. Relative attribute importance (RAI) (0-100%) was calculated for aggregate efficacy and safety attributes. Latent class analysis (LCA) explored preference heterogeneity and differences in respondent characteristics.

Results: In total, 201 oncologists completed the discrete choice experiment. Oncologists emphasized the efficacy over safety (RAI = 47.0% vs 39.0%). LCA identified two classes, placing similar importance on efficacy (RAI = 44.5% vs 48.2%) and safety (RAI = 39% vs 41.2%), but preferring different levels in five attributes. Class 1 oncologists (61%) preferred 3-year PFS of 64% over 43-46%, while Class 2 oncologists (39%) did not differentiate. Conversely, Class 2 focused on iDOR.

Conclusion: We identified two oncologist groups with distinct preferences for treatment attributes. Given various 1 L ALK+ mNSCLC treatments, clinical decision-making balances multiple objectives.

Background: This prospective, observational study evaluated the real-world safety of osimertinib in a broad Chinese population with non-small cell lung cancer (NSCLC).

Methods: Chinese NSCLC patients who received osimertinib were enrolled and followed up for 12 months. The primary endpoint was the incidence of adverse drug reactions (ADRs).

Results: From 20 April 2020 to 1 August 2022, 1,700 patients were enrolled from 30 centers, with 706 (41.5%) patients ≥65 years old. Osimertinib was administered as first-line, second-line, third/later-line and adjuvant therapy in 44.9%, 34.2%, 14.3% and 4.5% of the patients, respectively. ADRs, adverse events (AEs), Grade ≥3 AEs, and serious AEs were reported in 627 (36.9%), 959 (56.4%), 165 (9.7%), and 102 (6.0%) patients, respectively. AEs of special interests occurred in 59 (3.5%) patients, with 41 (2.4%) and 19 (1.1%) reporting QTc prolongation and interstitial lung disease/pneumonitis-like events, respectively. The safety profiles in patients ≥65 years old and those usually not included in randomized clinical trials were similar to that in the total population.

Conclusion: This largest real-world safety study of osimertinib in China demonstrated that osimertinib was well-tolerated in a broad NSCLC population, including patients usually not included in randomized clinical trials, without new safety signals identified.

Clinical trial registration: NCT03485326 (www.clinicaltrials.gov).

Background: Durvalumab-based regimens have improved outcomes compared with standard of care in unresectable hepatocellular carcinoma (uHCC) and advanced biliary tract cancer (aBTC) clinical trials. Here we describe the protocol for the LIVER-R study, which will evaluate long-term outcomes with durvalumab-based regimens in patients with hepatobiliary cancers in real-world settings.

Methods: LIVER-R (NCT06252753) is an observational study aiming to initially enroll ~2500 adults with uHCC or aBTC from ~179 sites in 22 countries. Patients treated with durvalumab-based regimens as part of routine clinical practice or a global early access program will be included. The primary outcome is overall survival. Secondary outcomes include duration of treatment, progression-free survival, treatment patterns and safety. Data will be collected at baseline and every 6 months. The study will include a baseline period of up to 5 years before index date (initiation of first-line durvalumab-based regimen) and a follow-up period from index until death, loss to follow-up, withdrawal, or study end. Study variables will be analyzed descriptively; time-to-event outcomes will be analyzed using the Kaplan-Meier method.

Conclusions: LIVER-R will produce a large, global, real-world standardized dataset of patients with uHCC or aBTC treated with a durvalumab-based regimen, providing insights into real-world clinical practice.

Clinical trial registration: www.clinicaltrials.gov identifier is NCT06252753.