A phase II study evaluated a corticosteroid-free regimen (olanzapine, netupitant, and palonosetron) for the treatment of chemotherapy-induced nausea and vomiting. The results showed control rates comparable to those of standard protocols, demonstrating its feasibility without dexamethasone. ■ Evaluation of a corticosteroid-free antiemetic regimen. ■ Primary endpoint: 46% nausea control. ■ Secondary endpoint: 68% emesis control. ■ Comparable to standard four-drug protocols.

Hypomethylating agents are frontline therapies for myelodysplastic neoplasms (MDS), yet clinical responses remain unpredictable. We conducted a phase 2 trial comparing injectable and oral azacitidine (AZA) administered over one or three weeks per four-week cycle, with the primary objective of investigating whether response is linked to in vivo drug incorporation or DNA hypomethylation. Our findings show that injection results in higher drug incorporation, but lower DNA demethylation per cycle, while global DNA methylation levels in mononuclear cells are comparable between responders and non-responders. However, hematopoietic stem and progenitor cells (HSPCs) from responders exhibit distinct baseline and early treatment-induced CpG methylation changes at regulatory regions linked to tissue patterning, cell migration, and myeloid differentiation. By cycle six-when clinical responses typically emerge-further differential hypomethylation in responder HSPCs suggests marrow adaptation as a driver of improved hematopoiesis. These findings indicate that intrinsic baseline and early drug-induced epigenetic differences in HSPCs may underlie the variable clinical response to AZA in MDS.

Poly (ADP-ribose) polymerase inhibitors (PARPi) exploit DNA repair deficiency in germline BRCA1 and BRCA2 pathogenic variant (gBRCAm) cancers. Haematological toxicity limits chemotherapy-PARPi treatment combinations. In preclinical models we identified a schedule combining olaparib and carboplatin that avoids enhanced toxicity but maintains anti-tumour activity. We investigated this schedule in a neoadjuvant, phase II-III, randomised controlled trial for gBRCAm breast cancers (ClinicalTrials.gov ID:NCT03150576; PARTNER). The research arm included carboplatin (Area Under the Curve 5, 3-weekly); paclitaxel (80 mg/m2, weekly) day 1, plus olaparib (150 mg twice daily) day 3-14 (4 cycles), followed by anthracycline-containing chemotherapy (3 cycles); control arm gave chemotherapy alone. The primary endpoint, pathological complete response rate, showed no statistical difference between research 64.1% (25/39); control 69.8% (30/43) (p = 0.59). However, estimated survival outcomes at 36-months demonstrated improved event-free survival: research 96.4%, control 80.1% (p = 0.04); overall survival: research 100%, control 88.2% (p = 0.04) and breast cancer specific survival: research 100%, control 88.2% (p = 0.04). There were no statistical differences in relapse-free survival and distant disease-free survival, both were: research 96.4%, control 87.9% (p = 0.20). Similarly, local recurrence-free survival and time to second cancer were both: research 96.4%, control 87.8% (p = 0.20). The PARTNER trial identified a safe, tolerable schedule combining neoadjuvant chemotherapy with olaparib. This combination demonstrated schedule-dependent overall survival benefit in early-stage gBRCAm breast cancer. This result needs confirmation in larger trials.

Transarterial chemoembolization (TACE) is considered unsuitable for hepatocellular carcinoma (HCC) that exceeds up-to-7 criteria. Balloon-occluded alternative infusion of cisplatin solution and gelatin particles of transarterial chemoembolization (BOAI-TACE) has shown promise in the treatment of HCC and preservation of liver function. This prospective, single-arm study enrolled patients with HCC beyond up-to-7 criteria from five hospitals. The primary endpoint was objective response ratio (ORR) for BOAI-TACE, according to response evaluation criteria in cancer of the Liver (RECICL), at 2 months after treatment. Eighteen patients were enrolled in this study. Fourteen patients achieved response, resulting in an ORR of 77.8% (95% confidence interval [CI] 54.3-91.5%) according to both RECICL and modified response evaluation criteria in solid tumor (mRECIST) guidelines, meeting the primary endpoint. Disease control rate was 88.9% (95% CI 66.0-98.1%). No worsening of either Child-Pugh or albumin-bilirubin (ALBI) scores was observed. No serious adverse events were recorded, indicating that BOAI-TACE retains utility even in severe HCC cases while preserving liver function.

Background Transarterial chemoembolization (TACE) is regarded as the first-line treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC). However, the optimal chemotherapeutic agent loaded in TACE remains controversial. Purpose To compare the efficacy and safety of idarubicin and epirubicin as loaded drugs in drug-eluting bead (DEB)-TACE in patients with BCLC stage B HCC. Materials and Methods In this open-label, phase IV trial, patients with BCLC stage B HCC were recruited from four centers from August 2020 to October 2022 and randomly assigned (at a one-to-one ratio) to undergo idarubicin DEB-TACE or epirubicin DEB-TACE. The primary end point was progression-free survival (PFS), which was measured from the time of randomization to the time of progression or death from any cause. The efficacy analysis was conducted on an intention-to-treat basis, and only participants who received treatment were included in the safety analysis. Results A total of 239 participants (median age, 57 years; IQR, 50-66 years; 210 male) were randomly assigned to the idarubicin group (n = 120) or the epirubicin group (n = 119). The primary analysis cutoff for PFS was March 1, 2023, with 167 events observed (70%; idarubicin group, 85 events; epirubicin group, 82 events). The median PFS was 10.8 months and 8.7 months in the idarubicin and epirubicin groups, respectively (hazard ratio [HR], 0.61; 95% CI: 0.44, 0.84; P = .002). The HR for median overall survival (OS) was 0.53 (95% CI: 0.31, 0.88), with OS rates of 81.5% and 77.3% at 12 months and 71.8% and 54.0% at 24 months for the idarubicin and epirubicin groups, respectively. The objective response rates were 70.8% and 57.1% for the idarubicin and epirubicin groups, respectively (P = .03). There was no evidence of a between-group difference in incidence of adverse events, including hematologic toxicity. No treatment-related deaths were observed. Conclusion Idarubicin DEB-TACE increased survival in participants with BCLC stage B HCC, without an increase in the incidence of any adverse events. Clinical trial registration no. ChiCTR2000034758 © RSNA, 2025 Supplemental material is available for this article.

In the phase 3 EMPOWER-Lung 1 study, first-line cemiplimab monotherapy provided significant survival benefit versus chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. This exploratory subgroup analysis investigated the clinical outcomes of cemiplimab treatment in patients with advanced NSCLC with brain metastases.

To evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary antitumour activity of AMG 404, a fully human IgG1 monoclonal antibody targeting programmed cell death-1, in patients with advanced solid tumours.

Anti-PD-1 monotherapy has shown limited clinical efficacy in patients with relapsed/refractory acute myeloid leukemia (r/r AML). Our study aimed to analyze the effectiveness and safety of combining tislelizumab with a hypomethylating agent (HMA) plus CAG regimen in treating patients with r/r AML, with an increased sample size and in comparison, with a historical control group for more reliable data support (ClinicalTrials.gov identifier NCT04541277).

Initial results of this study, reported after a median follow-up close to 4 years, demonstrated improved time to initiation of new treatment (TTNT) for patients with advanced stage, asymptomatic, low tumour burden follicular lymphoma who received early rituximab monotherapy when compared with watchful waiting. Given the long natural history of follicular lymphoma, the trial was extended to further assess TTNT with longer follow-up. Mature data are presented here.

The β2 common integrin subunit CD18 is essential for leukocyte-endothelial adhesion and extravasation to inflamed or infected tissue. Damaging variants in ITGB2, which encodes CD18, cause leukocyte adhesion deficiency type I (LAD-I), an inborn error of immunity that leads to frequent life-threatening infections and a high risk of death among affected children. Allogeneic hematopoietic stem-cell transplantation (HSCT) represents a curative treatment but is limited by donor availability, a high incidence of graft-versus-host disease, and graft failure.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prevalent adverse effect of chemotherapy agents that is estimated to be present in 2/3 of patients who receive neurotoxic chemotherapy. In 30-40% of these patients, CIPN signs and symptoms can persist for months or years post-treatment. Recent studies have supported exercise as a feasible and possibly effective intervention for CIPN; however, more rigorous studies are needed to confirm feasibility, estimate efficacy, and clarify risk. In response, we developed an innovative virtual exercise-based rehabilitation program (EX-CIPN) for cancer survivors with persistent CIPN.

Neoadjuvant treatment of bladder cancer is evolving, with immunotherapy demonstrating promising activity. PARP inhibition combined with immune activation has been proposed as a synergistic strategy. We conducted a comprehensive molecular characterization of tumors treated with this combination in the neoadjuvant setting to provide crucial results for rational development.

Low-dose tamoxifen 5 mg/day (babytam) for 3 years can decrease the incidence of new breast cancer events in women with breast intraepithelial neoplasia by 42% with limited toxicity, which provides a new treatment option for these disorders. However, predictive biomarkers of babytam efficacy are lacking. We studied whether baseline levels of insulin-like growth factor-1 (IGF-I), IGF-binding protein-3 (IGFBP-3), estradiol, and sex hormone-binding globulin (SHBG) and their ratios predict babytam efficacy on breast cancer events in a preplanned secondary analysis.

Peripheral T-cell lymphoma (PTCL) is an aggressive malignancy with limited treatment options and poor prognosis, particularly for relapsed or refractory (r/r) patients. HH2853, a novel dual inhibitor of EZH1/2, has previously demonstrated clinical benefits in solid tumors. Here, we report safety and efficacy data from a phase Ib trial of HH2853 in r/r PTCL.

HP518 is an oral PROteolysis TArgeting Chimera (PROTAC) protein degrader targeting the wild-type androgen receptor (WT-AR) and mutant AR ligand-binding domain (AR-LBD). A multicenter, first-in-human, open-label Phase 1 dose escalation study was conducted in patients with metastatic castration-resistant prostate cancer (mCRPC) to evaluate the safety, pharmacokinetics, and anti-tumor activity of HP518. Twenty-two patients with mCRPC with disease progression on at least 1 novel androgen receptor pathway inhibitor (ARPI) and ≤ 1 line of chemotherapy received HP518 once daily orally in sequential cohorts. Patients were not selected for AR-LBD mutations. Objectives were to assess safety, tolerability, maximum tolerated dose, pharmacokinetics (PK), as well as efficacy by PSA50 response and radiographic response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Prostate Cancer Working Group 3 (PCWG3) criteria. Exploratory objectives included genomic profiling using cell-free DNA. The majority of treatment-emergent adverse events (TEAEs) were Grade 1 or 2. The most common AEs were nausea and vomiting, fatigue, constipation, diarrhea, and decreased appetite. Only one (vomiting) out of 10 serious adverse events (SAE) was considered drug-related. No patient experienced a dose-limiting toxicity (DLT), and no AEs led to dose reduction or study discontinuation. Following multiple dosing of HP518, the PK appeared to plateau showing a less than dose-proportional relationship between exposure and dosage. Two patients demonstrated a partial response, and three patients showed a PSA50 response. In this initial Phase 1 study, HP518 demonstrated an acceptable safety profile and responses in a limited subset of mCRPC patients with progression after ARPI warranting further investigation. ClinicalTrials.gov Identifier: NCT05252364.

Mosunetuzumab, a CD20 × CD3 T-cell-engaging bispecific antibody, redirects T cells to eliminate malignant B cells. The purpose of YO43555 was to assess the pharmacokinetics (PK), safety, tolerability, and efficacy of mosunetuzumab as a single agent in Chinese patients with relapsed/refractory follicular lymphoma (R/R FL). The impact of ethnicity/region on the PK disposition of mosunetuzumab was assessed by non-compartmental analysis (NCA) as well as a population PK (popPK) approach. A previously established popPK model for intravenous mosunetuzumab, built from the global Phase I/II study GO29781, was externally validated with the PK data from study YO43555. Results from the PK analysis showed that the global popPK model adequately captured the individual PK of the Chinese population. The model predicted mosunetuzumab exposure metrics in Chinese patients were similar to those observed in Asian patients in the GO29781 R/R FL subpopulation with the same dose regimen, while the exposure differences between Chinese and Non-Asians from the global population were < 20%. An overlay of the exposure levels for Chinese patients on the established E-R relationship in global patients indicated that the mosunetuzumab exposure of Chinese patients remained within the established bounds for clinical safety and efficacy. The cytokine biomarkers IL-6 and TNF-α showed similar time-course patterns of release as observed in globally enrolled patients. In summary, mosunetuzumab PK disposition did not show significant ethnic sensitivity that would impact patient outcomes. Therefore, dose adjustment of the globally approved mosunetuzumab regimen is not warranted for Chinese patients with R/R FL. Trial Registration: ClinicalTrials.gov identifier: NCT02500407.

Background: To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex® in Chinese patients with premenopausal breast cancer. Methods: From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex® every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results: A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex®. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex®. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex® group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion: LY01005 is as effective as Zoladex® in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

D07001-F4 is an absorption-enhanced oral gemcitabine developed in liquid formulation and adjusted to D07001-softgel capsules. We conducted 2 phase 1 studies to evaluate the dose-limiting toxicity (DLT), pharmacokinetics (PK), and maximum tolerated dose (MTD) of the 2 formulations of D07001 in patients with advanced solid tumors.

Immune checkpoint inhibitors (ICIs) improved survival in patients with locally advanced or metastatic urothelial carcinoma (la/mUC). Patient-reported symptoms in this context were poorly studied. The study aimed to compare symptom severity between patients and clinicians.

Immune checkpoint inhibitors (ICIs) have significantly improved the overall survival for patients with different solid tumors. However, there is an urgent need for predictive biomarkers to identify patients with metastatic melanoma who do not benefit from treatment with ICIs, to prevent unnecessary immune related adverse events (irAEs). Electronic noses (eNoses) showed promising results in the detection of cancer as well as the prediction of response outcome in patients with cancer. In this feasibility study, we aimed to investigate whether the breath pattern measured using eNose can be used as a simple biomarker to predict clinical benefit to first-line treatment with ICIs in patients with metastatic melanoma.