Enfortumab vedotin, a fully human monoclonal antibody-drug conjugate (ADC) directed to Nectin-4, prolonged overall survival (OS) versus standard chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma (mUC) previously receiving a programmed cell death protein 1/ligand 1 (PD-1/L1) inhibitor and platinum-based chemotherapy in the pivotal, phase 3 EV-301 clinical trial, supporting global approvals of enfortumab vedotin monotherapy. This bridging study was the first to evaluate enfortumab vedotin monotherapy in previously treated Chinese patients with locally advanced or mUC.

The use of first-line poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is increasing in advanced ovarian cancer. Understanding the efficacy of first subsequent therapy (FST) in patients experiencing disease progression in the first-line setting is important to optimize postprogression treatments. We evaluated the efficacy of FST in patients from PAOLA-1/ENGOT-ov25 (NCT02477644) who received first-line olaparib maintenance.

Patients with locoregionally advanced nasopharyngeal carcinoma with a high pretreatment plasma concentration of Epstein-Barr virus (EBV) DNA remain at high risk for recurrence after concurrent chemoradiotherapy. This study aimed to compare the efficacy and safety of neoadjuvant-adjuvant treatment with the PD-1 inhibitor toripalimab and concurrent chemoradiotherapy versus placebo and concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma.

Sulforaphane (SFN) is a naturally occurring isothiocyanate associated with various health benefits, including reduced cancer risk, and has been extensively explored as a potential therapeutic. However, its inherent instability presents challenges in formulation, storage, and administration as a medicinal product. SFX-01 (Sulforadex®) is a patented synthetic form of d,l-SFN stabilized within a biologically inert alpha-cyclodextrin complex.

To determine the efficacy and safety of proton beam irradiation (PBI) and anti-vascular endothelial growth factor (anti-VEGF) therapy for polypoidal choroidal vasculopathy (PCV)/ aneurysmal type 1 macular neovascularization (AT1).

The use of complementary therapies to relieve the side effects of chemotherapy in lung cancer patients is becoming increasingly popular. Practices from traditional Chinese medicine, such as acupoint massage and five-tone therapy, have demonstrated potential in alleviating symptoms such as nausea and vomiting experienced during chemotherapy.

The phase II PRIMMO trial investigated a pembrolizumab-based regimen in patients with recurrent and/or metastatic cervical (CC) or endometrial (EC) carcinoma who had at least one prior line of systemic therapy. Here, exploratory studies of the gut microbiome (GM) are presented.

Pharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none are US Food and Drug Administration-approved for adults.

Monitoring metabolites of tamoxifen, such as endoxifen, has been suggested as a strategy to ascertain therapeutic effect of tamoxifen therapy, but clinical guidelines are missing. Herein, we aim to investigate the outcome of endoxifen concentrations of low-dose tamoxifen, using change in mammographic breast density as a proxy for therapy response.

Radiotherapy may enhance antitumor immune responses by several mechanisms, including induction of immunogenic cell death. We performed a phase 2 study of pembrolizumab with re-irradiation in patients with recurrent glioblastoma.

Treatment of nosebleeds in Osler-Weber-Rendu disease (OWRD) is a therapeutic challenge. Intranasal anti-angiogenic sprays are a promising solution, requiring scientific validation, leading us to conduct the present study.

In patients with metastatic melanoma who respond to anti-PD-1 therapy, the proliferation of intra-tumour CD8+ T cells is directly correlated with the clinical response, making tumour-infiltrating lymphocytes (TILs) a treatment of interest in combination with a PD-1 inhibitor, which is the undisputed gold standard in the management of metastatic melanoma. The aim of this trial was, therefore, to evaluate the safety and efficacy of sequential combination therapy consisting of nivolumab (a PD-1 inhibitor) and TILs adoptive T cells in patients with metastatic melanoma.

Intravitreal injections with anti-vascular endothelial growth factor (VEGF) drugs can slow progression in neovascular age-related macular degeneration (nAMD). Best spectacle-corrected visual acuity (BSCVA) and/or central retinal thickness (CRT) are common barometers of efficacy of this treatment. However, BSCVA does not accurately measure reading ability, which is often severely impacted by nAMD. Since most studies on the effect of intravitreal anti-VEGF injections on reading ability in nAMD have limitations, we conducted an open-label nonrandomized non-blinded self-controlled clinical trial using Radner Charts, a standardized, validated tool for measuring reading ability.

Increasing the response rates of immune checkpoint inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC) presents a significant challenge. ESK981 is a multi-tyrosine kinase and PIKfyve lipid kinase inhibitor that augments immunotherapeutic responses. In this phase II study, ESK981 was combined with the PD-1 blocking monoclonal antibody nivolumab to test for potentially improved response rates in patients with mCRPC who have progressed on androgen receptor (AR)-targeted agents and chemotherapy. Eligible patients received ESK981 orally once daily for five consecutive days, followed by a two-day break. Patients were also treated with nivolumab intravenously on Day 1 of each 28-day cycle. The primary endpoints were a 50% reduction in prostate-specific antigen (PSA50), and safety. Secondary endpoints included radiographic progression free survival (rPFS) and overall survival (OS). Additional investigations included whole exome sequencing in patients. Ten patients were enrolled. The maximum PSA decline from baseline of 14% was achieved in only one patient. Grade 3 treatment-related adverse events (AEs) included fatigue, anemia, and lymphopenia. There were no Grade 4 events. The median rPFS was 3.7 months (95% CI, 1.6-8.4). The median OS was 9.6 months (95% CI, 1.8-22.4). The study was terminated due to futility after 10 patients. Whole exome sequencing identified AR amplification in 63% of patients (5/8). ESK981 + nivolumab showed no antitumor activity in patients with AR-positive (AR+) mCRPC. Further evaluation of ESK981 combined with the PD-1 inhibitor nivolumab in AR + mCRPC patients is not warranted. (Trial registration: ClinicalTrials.gov NCT04159896. Registration date: November 12, 2019.).

Chemo-endocrine therapy can lead to various side effects associated with ovarian dysfunction. Predicting menstrual recovery is necessary to discuss the treatment-related issues regarding fertility and premature menopause with patients.

This was a multicenter, single-arm, open-label, phase Ib/II study (NCT04255576), aimed to evaluate the efficacy and safety of JMT103 in patients with unresectable or surgically-challenging giant cell tumor of bone (GCTB). JMT103 (2 mg/kg) was administered subcutaneously every four weeks, with loading doses on days 8 and 15. The primary endpoint was the objective tumor response rate (OTR) based on best response, defined as the proportion of patients who achieved elimination of at least 90% of the giant cells or radiologic complete or partial response per the modified Inverse Choi density/size (mICDS) or modified European Organization for Research and Treatment of Cancer (mEORTC) within 12 weeks. Secondary endpoints included objective response rate (ORR) per mICDS and mEORTC, and safety. A total of 139 patients were enrolled, and 135 were analyzed for efficacy. OTR, determined by the independent review committee (IRC) was 93.3% (95% CI 87.7-96.9). Treatment-related adverse events occurred in 90 (64.7%) patients, with hypophosphatemia and hypocalcemia being the most common. No serious treatment-related adverse events were observed. Thus, JMT103 demonstrates potential as a therapeutic option for GCTB.

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant clinical issue that affects patients' quality of life and can limit the dosing of chemotherapeutic agents. N-acetylcysteine (NAC) has been proposed as a potential chemoprotective agent against CIPN due to its antioxidant properties. This study aimed to investigate the efficacy of oral NAC in preventing and controlling taxane-induced neuropathy in patients with breast cancer.

The MTOR inhibitors have demonstrated antiviral properties, and prior non-randomized studies have suggested they may have a suppressive effect on BKPyV replication. Here, in this randomized, multicenter, controlled trial (BKEVER study), we sought to evaluate the impact of everolimus (EVR) in facilitating the clearance of BKPyV compared to simply reducing immunosuppression among kidney transplant recipients (KTRs). All together, 130 KTRs presenting with BKPyV DNAemia were randomized 1:1 into two groups. The EVR group, in which mycophenolate mofetil (MMF) was replaced by EVR along with a decrease in calcineurin inhibitor trough levels and secondly the MMF group, in which the MMF dose was decreased by half along with a similar lowering of calcineurin inhibitor levels. The primary endpoint was the proportion of patients achieving viral clearance at six months. Secondary endpoints included the kinetics of BKPyV replication over time, the incidence of BKPyV-associated nephropathy, kidney graft function, the incidence of kidney graft rejection, and medication tolerability over two years. Significantly, BKPyV clearance was achieved in 55.7% of patients in the EVR group compared to 81.3% of patients in the MMF group at six months. The reduction in BKPyV DNA load was significantly more rapid in the MMF group. Calcineurin inhibitor trough levels were within expected target ranges and did not differ meaningfully between the two groups from randomization through month six. Two grafts were lost, and four patients died. Eleven patients in the EVR group and six patients in the MMF group developed biopsy-proven BKPyV nephropathy. Thus, in KTRs with BKPyV DNAemia, replacing MMF with EVR along with lowering calcineurin inhibitor levels did not lead to more frequent or faster clearance of BKPyV.

Cachexia affects approximately 50-80 % of advanced cancer patients, particularly those with gastric cancer (GC). Therefore, early detection of cachexia is essential to prevent its progression. Targeting the gut microbiota may be a promising approach for preventing and treating cachexia in patients with GC. Chemotherapy significantly reduced gut microbiota diversity in GC patients. Specifically, the abundance of bacterial genera such as Bacteroides, Streptococcus, and Prevotella was increased in the gut of patients postchemotherapy, which was closely associated with the development of cachexia. Serum metabolic analysis revealed a strong link between specific microbes and metabolite in patients with chemotherapy-induced GC cachexia. We further constructed a random forest model based on the top 6 genera in terms of abundance for the prediction of chemotherapy-related GC cachexia development; this model had an area under the receiver operating characteristic curve (AUC) of 93.5 % [95 % confidence interval (CI), 86.6 %-100 %], with a specificity and accuracy above 75 %. Additionally, we identified Enterotoxin Bacteroides fragilis (ETBF) as a key factor in chemotherapy-induced GC cachexia. In an in vivo GC model, the colonization of ETBF in the intestines of mice significantly accelerated the muscle and adipose tissue consumption induced by chemotherapy, resulting in cachexia symptoms. Furthermore, ETBF damaged the intestinal mucosal barrier by disrupting cell connections and attracting M1 macrophages, which advances GC cachexia. In conclusion, our findings indicate that gut microbiota imbalance is crucial in GC cachexia development, suggesting potential biomarkers for early diagnosis. Clinical trial registration: http://www.chictr.org.cn, Identification No: ChiCTR2200064547.

Lymphangioleiomyomatosis is an ultra-rare disease mainly affecting women of childbearing age. The MILES trial showed the efficacy of sirolimus, an mTOR inhibitor, in stabilising lung function in patients with lymphangioleiomyomatosis. Drug toxicity and development of resistance are potential limitations of therapy with sirolimus. Nintedanib is a multikinase inhibitor that inhibits PDGFR, which is active in human and murine lymphangioleiomyomatosis lesions. We aimed to investigate the activity and safety of nintedanib in patients with lymphangioleiomyomatosis.