Patients with BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) face a high risk of disease progression. While radical cystectomy (RC) remains the recommended standard of care, many patients are unfit for or unwilling to undergo radical surgery, leading to bladder-sparing strategies spreading in real-world practice. This study aims to describe the oncological outcomes of patients diagnosed with BCG-unresponsive NMIBC treated with gemcitabine/docetaxel (Gem/Doce), electromotive drug administration of mitomycin C (EMDA/MMC), further BCG, or upfront RC. We included patients diagnosed with BCG-unresponsive NMIBC treated across 21 European centers (2009–2024) with either intravesical Gem/Doce, EMDA/MMC, further BCG, or upfront RC. Cumulative incidence curves were used to estimate the risk of recurrence, high-grade recurrence, progression, cancer-specific and overall mortality. Multivariable Cox regression models were used to assess the association between treatment type and the risk of recurrence and progression. Of the 361 patients, 104 (28
Propofol is the most frequently used hypnotic during rapid sequence induction in patients at risk of pulmonary aspiration of gastric contents worldwide. Its most common side effect is to induce hypotension due to dose-dependent vasoplegia. Ketamine is an alternative with pharmacological hemodynamic stability but a higher risk of postoperative delirium. Ketofol, an equimolar combination of these two hypnotics, has recently been proposed in this setting. The objective of this study is to demonstrate the superiority of ketamine (or ketofol) compared to propofol, in association with a neuromuscular blocking agent, for achieving tracheal intubation without hypotension in patients undergoing surgery under general anesthesia and at risk of pulmonary aspiration of gastric contents. The HyPnotiKs study is a multicenter, open-labeled, superiority, randomized controlled trial comparing ketamine (2 mg/kg), propofol (2 mg/kg), and ketofol (1 mg/kg each) for rapid sequence induction in 1218 adult surgical patients requiring tracheal intubation during general anesthesia. Enrollment started in April 2025 in 20 French anesthesia units. The expected date of the final follow-up is May 2027. The primary outcome is the proportion of successful tracheal intubation at the first attempt and without major hypotension. A hierarchical procedure is planned to compare the three arms. Intention-to-treat principle will be applied. The HyPnotiKs study protocol has been approved by the ethics committee of the Comité de Protection des Personnes Sud Méditerranée V and will be carried out in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals. The HyPnotiKs study is the first randomized controlled trial powered to investigate whether ketamine, ketofol, or propofol is the hypnotic of first choice for rapid sequence induction of anesthesia in patients with a full stomach, considering successful tracheal intubation without hypotension. ClinicalTrials.gov NCT06733129. Registered on December 2024.
e16441 Background: Pancreatic ductal adenocarcinoma is one of the most lethal malignancies with a 5-year survival rate under 5%. Locally advanced pancreatic ductal adenocarcinoma (LAP) represents 30-40% of cases at the diagnosis, with an overall survival around 15 months. Optimizing chemotherapy in LAP is still a huge challenge. A concomitant inhibition of epithelial mesenchymal transition (EMT) process may potentiate chemotherapy efficacy and decrease the development of resistances. Netrin-1 is upregulated in many metastatic cancers including 60% of pancreatic cancer and promotes tumor invasiveness and metastases development through EMT induction. NP137, a first-in-class anti-Netrin-1 monoclonal antibody, has shown in phase I study the ability to inhibit EMT, potentially overcoming resistance (Cassier et al., Nature, 2023). The goal of LAP-NET1 (NCT05546853) is to evaluate the safety and efficacy of the combination of modified FOLFIRINOX with anti-Netrin-1 targeting (NP137). Methods: LAP-NET1 is a phase 1b multicentric trial studying the combination of modified FOLFIRINOX with NP-137 every 2 weeks for 12 cycles in patients naive of systemic treatment with LAP according to National Comprehensive Cancer Network criteria. A safety lead-in phase will initially enroll 3-12 patients to confirm the recommended dose of NP137 (14 or 9 mg/kg) according to a 3+3 de-escalation protocol, followed by an expansion phase of 40 patients. The primary endpoint is the proportion of patients experiencing adverse events (AEs) of any grade and grade 3/4 AEs (CTCAE v 5.0) related to the experimental treatment at 6 months. Secondary endpoints are best overall objective response according to RECIST 1.1, 12-month progression-free survival (PFS-12m), 12-month overall survival (OS-12m), surgical resection rate, quality of life (EORTC QLQ-C30), time to deterioration and ancillary outcomes based on spatial transcriptomic and classic bulk RNA sequencing. Clinical trial information: NCT05546853 .
The prognosis of elderly patients with Hodgkin lymphoma (HL) unfit for conventional chemotherapy remains poor. We report the results of the LYSA phase II NIVINIHO trial in treatment-naive HL patients aged ≥ 61 years with comorbidities contraindicating standard chemotherapy. Treatment included an induction phase with nivolumab alone, followed by a consolidation phase: either nivolumab monotherapy for patients with early complete metabolic response or nivolumab plus vinblastine for patients with stable disease or partial response. The primary objective of the study was the complete metabolic response (CMR) rate at the end of treatment. From August 2018 to April 2020, 64 patients were enrolled. Median age was 75.0 (range, 62 to 91) years, Ann Arbor stage was advanced (stage III-IV) in 75.0% of patients. At end of nivolumab induction, 11 patients (17.2%) achieved CMR and were consolidated with nivolumab alone, 23 (35.9%) patients obtained PMR or SD and received vinblastine plus nivolumab. Among the 56 evaluable patients, 16 (28.6%) achieved CMR at the end of treatment. With a median follow-up of 24.4 months (range, 0.9 to 35.2), median progression-free survival (PFS) was 9.8 months (95% confidence interval [CI], 4.2 to 12) while the 2-year overall survival (OS) rate was 74.1% (95%CI, 58.9% to 84.4%). Thirtytwo patients (50%) experienced grade ≥ 3 adverse events (AEs). Nivolumab-related adverse events led to treatment discontinuation in 19 patients (29.7%). Our results show that nivolumab can be administrated to elderly, frail patients unfit for classical chemotherapy; however, the objective response rate with monotherapy remains low. Trial registration number: NCT03580408.
