To compare the efficacy and safety of gonadotropin-releasing hormone agonist combined with an aromatase inhibitor versus oral progestins as fertility-sparing treatment in patients with endometrial carcinoma or atypical endometrial hyperplasia.

Prostate-specific antigen (PSA) testing to screen for prostate cancer is controversial. An alternative approach, Stockholm3, combines PSA, plasma protein biomarkers, polygenic risk, and clinical factors into a multivariable risk score.

This analysis reports efficacy and safety data in the subgroup of Black patients from the ARANOTE phase 3 trial.

Several ultrasound risk stratification systems have been developed mainly with the aim of identifying benign lesions and thereby avoiding unnecessary fine needle aspiration (FNA) cytology. This randomized controlled trial assessed whether the use of an ultrasound risk stratification system improved identification of lesions requiring surgical treatment.

The combination of olaparib plus radium-223 improved progression-free survival in patients with metastatic castration-resistant prostate cancer with bone metastases (BM) in the multicenter, randomized, phase 2 COMRADE trial (NCT03317391). Here, the patient-reported outcome (PRO) analysis of this trial is reported.

Index lesion-focused ipsilateral systematic biopsy (iSB) has been proposed as a core-reduction alternative to MRI-targeted biopsy combined with systematic biopsy (TB + SB) for prostate cancer, but prospective multicenter validation is limited.

Primary central nervous system lymphoma (PCNSL) is a rare, highly aggressive form of non-Hodgkin lymphoma. Although initial responses to the guideline-recommended first-line high-dose methotrexate induction treatment are high, some patients have refractory disease and most experience relapse. Approved therapies for relapsed or refractory (R/R) PCNSL are limited in the US, and there are none in Europe, creating an urgent unmet need for effective treatments. Tirabrutinib is a highly potent and selective second-generation Bruton tyrosine kinase inhibitor approved in Japan, Taiwan, and South Korea for patients with R/R PCNSL. Here, we describe the rationale and design of IGNITE (ONO-4059-17), an ongoing, phase III, multiregional, open-label, randomized study of tirabrutinib vs rituximab and temozolomide combination therapy in R/R PCNSL. The primary endpoint is progression-free survival based on blinded independent review committee (BIRC) per International PCNSL Collaborative Group (IPCG) criteria. Key secondary endpoints are overall response rate based on BIRC per IPCG criteria and overall survival. Safety will be assessed by the incidence and severity of treatment-emergent adverse events.Clinical trial registration: www.clinicaltrials.gov identifier is NCT07104032.

Hepatocellular carcinoma (HCC) is a lethal cancer with an increasing burden. Few clinical trials have evaluated preventive strategies for HCC in high-risk patients with liver cirrhosis. Observational studies show that statins are associated with a reduced HCC risk although a causal link has yet to be established. This multicenter randomized double-blinded, placebo-controlled phase II trial of 40 mg/day oral simvastatin to reduce the likelihood of hepatocarcinogenesis was conducted at four sites in the United States. The primary outcome was the change in serum α-fetoprotein (AFP)-L3% from baseline to 6 months. Secondary biomarker endpoints include changes in serum AFP, serum IL6, serum deoxycholic acid, liver stiffness, Model for End-Stage Liver Disease score, and Fibrosis-4 index score. Comparisons were made using paired t tests or the Wilcoxon rank-sum test. Forty-five participants completed the intervention and final study assessments [mean age, 58 years; female, 42%; Asian, 2.2%; Black or African American, 11%; White, 87%; Hispanic or Latino, 51%; Child-Pugh (CP) A, 69%; CP B, 16%]. Of 45 participants, 10 (22%) had detectable AFP-L3%, which did not differ between the intervention arms. Serum IL6 levels, detectable in all participants, decreased significantly in the simvastatin group compared with the placebo group (P = 0.02). The number and grade of adverse events did not differ between groups. In this randomized controlled trial, simvastatin was well tolerated in patients with liver cirrhosis but did not result in a decrease in AFP-L3%, potentially owing to the low number of participants with detectable AFP/AFP-L3%. Simvastatin did result in a decrease in IL6, offering one potential anticancer mechanism of simvastatin in the setting of cirrhosis.

New therapeutic strategies for patients with therapy-refractory metastatic urothelial carcinoma (mUC) are still needed. In the phase I-II ICRA trial, a multicenter, open-label, phase Ib-II clinical trial (NCT03871036), we evaluated whether paclitaxel plus tremelimumab, with or without durvalumab, could induce a tumor response in mUC following platinum chemotherapy and immune checkpoint inhibition (ICI). Patients were randomized between three arms: A (n = 20) paclitaxel plus T750mg; B (n = 12) paclitaxel plus T300mg plus D1500mg; C (n = 12) T750mg. The primary outcome, objective response rate, was met with 26% in arm A (88% CI = [14,36%]) versus 17% (88% CI = [3,42%]) in arm B and 8% (88% CI = [0.3,33%]) in arm C. Secondary outcomes included safety, duration of response and survival. Grade 3-4 treatment-related adverse events occurred in (A) 45%, (B) 75%, and (C) 25% of patients. Murine experiments showed attenuated tumor outgrowth for paclitaxel plus anti-CTLA-4 compared to monotherapy with either agent. Transcriptomic analyses showed upregulation of inflammation signatures in on-treatment tumor tissue biopsies. This study demonstrated encouraging antitumor activity in therapy-refractory mUC treated with paclitaxel plus high-dose anti-CTLA-4 and suggests immune induction may still be possible after failure to anti-PD-(L)1 therapy.

Phosphoinositide 3-kinase (PI3K) pathway, involved in obesity-related signalling, may influence efficacy and toxicity of PI3K inhibitors (PI3Ki). We explored associations between body mass index (BMI) and objective response rate (ORR), safety, molecular features, and breast density in the LORELEI trial.

Advanced head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, particularly in resource-limited settings with restricted access to targeted or immune therapies. We evaluated whether adding triple oral metronomic chemotherapy (OMCT; erlotinib, celecoxib, methotrexate) to paclitaxel-carboplatin (PC) improves overall survival (OS) in patients with platinum-sensitive, unresectable advanced HNSCC. This was a single-center, investigator-initiated, prospective, randomized, open-label, phase III superiority trial conducted at a tertiary cancer center in North India.

IntroductionThere is currently no biomarker for progression-free survival (PFS) for patients undergoing treatment for metastatic renal cell carcinoma (RCC). The aim of our study was to evaluate computed tomography perfusion (CTp) blood flow as an early marker of PFS in patients with mRCC treated with targeted agents.MethodsAssociations between CTp blood flow and PFS were evaluated from prospective randomized evidence using univariable and multivariable Cox proportional hazards regression models with Harrell's concordance index (c-index) in patients with mRCC randomized to receive one of three targeted agents (everolimus, bevacizumab, or pazopanib). Analyses included baseline tumor CTp blood flow (BF0) and changes in blood flow after 8 weeks of therapy (ΔBF). Demographic and clinical prognostic factors (International mRCC Database Consortium [IMDC] risk score and ECOG performance) were included in the models as covariates.ResultsThe median PFS of the 55-patient cohort was 0.80 years (95% CI: 0.76-1.38 years), with no significant difference among the targeted agents. ΔBF and BF0 were significantly associated with PFS on univariable analysis (p=0.002 and p=0.013, respectively). Multivariable analyses incorporating all the above factors indicated that higher baseline BF0 (>166 mL/min/100g) and reduced ΔBF (<2.8%) were significantly associated with longer PFS (p<0.02).ConclusionCTp blood flow may have utility as independent prognostic and early surrogate markers of PFS in mRCC patients treated with targeted agents, surpassing clinical markers like IMDC risk classification. Higher baseline perfusion (BF0) delineates tumors responsive to targeted therapy, while reductions in perfusion (ΔBF) just 8 weeks after starting treatment are associated with longer PFS. These findings arise from randomized evidence, warranting further evaluations.

TRAILBLAZER is a proof-of-concept phase 2 study (ClinicalTrials.gov, NCT04580498) of neoadjuvant retlirafusp alfa (an anti-PD-L1/TGF-β bifunctional agent) in unresectable stage III non-small cell lung cancer (NSCLC) not harboring EGFR or ALK alterations. During induction, retlirafusp alfa was administered either with chemotherapy or as monotherapy, followed by surgery or radiotherapy as assessed by a local multidisciplinary team and consolidation retlirafusp alfa. Patients without high PD-L1 expression were allocated to retlirafusp alfa plus chemotherapy (arm A; n = 88); patients with high PD-L1 expression were randomly allocated at a 1:1 ratio to retlirafusp alfa combination (arm B; n = 9) or monotherapy (arm C; n = 10). In this updated analysis (data cutoff, March 24, 2025), the median follow-up was 39.4 months. The event-free survival (EFS) rate at 3 years was 50.5% (95% CI 39.0-61.0) in arm A + B and 77.1% (34.5-93.9) in arm C; the corresponding overall survival (OS) rates at 3 years were 68.3% (95% CI 57.5-77.0) and 87.5% (38.7-98.1), respectively. Among 27 patients who underwent surgery, the 3-year EFS and OS rates were 69.5% (95% CI 48.1-83.5) and 84.9% (64.5-94.0), respectively, versus 50.8% (36.5-63.4) and 70.4% (56.7-80.5), respectively, in radiotherapy-treated patients. The safety data were consistent with those in a previous report. With extended follow-up, the study regimen showed sustained survival benefits with no new safety signals. Patients who underwent surgery after induction treatment achieved clinically meaningful survival gains. Our findings support the use of neoadjuvant immunotherapy with a response-adapted surgical strategy as a promising approach for unresectable stage III NSCLC.

Novel, accessible treatment options, are needed for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Mosunetuzumab, a T-cell-engaging bispecific antibody, plus polatuzumab vedotin, an antibody-drug conjugate, (Mosun-Pola), represents a novel fixed-duration outpatient therapy. The phase III SUNMO study (NCT05171647) demonstrated superior efficacy of Mosun-Pola versus rituximab plus gemcitabine-oxaliplatin (R-GemOx) in patients with R/R LBCL, with a manageable safety profile. We report outcomes of a Japan subgroup analysis of the SUNMO study.

Although third-generation epidermal growth-factor receptor (EGFR)-tyrosine-kinase inhibitors (TKIs) are standard first-line therapies for patients with advanced EGFR-mutated non-small-cell lung cancer (NSCLC), their effectiveness is often limited by the emergence of drug resistance and subsequent disease progression. Given the previously established clinical efficacy and adverse event profile of aumolertinib, we aimed to evaluate the efficacy and adverse event profile of aumolertinib in combination with platinum-based chemotherapy versus aumolertinib monotherapy as first-line treatment for patients with locally advanced or metastatic NSCLC patients with EGFR-sensitive mutations.

In the phase III LAURA study, osimertinib demonstrated a statistically significant progression-free survival benefit versus placebo, and a generally tolerable safety profile, after definitive chemoradiotherapy (CRT) in unresectable stage III EGFR-mutated non-small cell lung cancer. We report in-depth safety data from LAURA.

Talquetamab, a bispecific antibody targeting GPRC5D and CD3, has led to durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma in phase 1-2 trials, with a limited effect on normal B cells.

Patients with cancer living in rural areas face unique challenges in accessing comprehensive care. Limited research has characterized disparities between patients living in more versus less remotely rural areas. This study investigated differences in health outcomes between patients with advanced cancer residing in more versus less rural areas.

Anthracycline-free regimens are needed for older adults with newly diagnosed diffuse large B-cell lymphoma (DLBCL). We aim to evaluate the efficacy and safety of fixed-duration epcoritamab monotherapy versus epcoritamab with lenalidomide in this patient population.

Avelumab first-line maintenance is the recommended treatment option for patients with advanced urothelial carcinoma (UC) without progression following platinum-based chemotherapy (PBC), based on the phase III JAVELIN Bladder 100 trial. High body mass index (BMI; ≥30 kg/m2) and diabetes mellitus (DM) are risk factors for bladder cancer. We report exploratory analyses from JAVELIN Bladder 100 in patients with high BMI or documented controlled DM at the time of random assignment.