Accurate preoperative radiological assessment is essential in breast-conserving surgery (BCS) to achieve clear margins while minimizing unnecessary healthy tissue excision. Discrepancies between radiological and pathological tumor size may contribute to re-excision. This study evaluated factors associated with radiology-pathology discordance and their impact on re-excision.

Vepdegestrant is an investigational, orally administered PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader being evaluated for the treatment of ER+/HER2- advanced breast cancer, with promising results in prior studies of Western and Japanese patients. Vepdegestrant had not been previously evaluated in Chinese patients.

High-dose selenium (Se) as selenomethionine (SLM) and sodium selenite (SS) can improve the efficacy of cancer therapies while reducing toxicity. Se-methylselenocysteine (MSC) is effective in preclinical models but has not been evaluated in cancer trials. This phase Ib randomised, double-blinded trial explored the safety, pharmacokinetics (PK) and selected pharmacodynamic (PD) mechanisms of MSC, SLM and SS to guide future trials. Nine participants with metastatic cancer took Se 1600 μg/day for 4 weeks, then 6400 μg/day for 4 weeks, as MSC, SLM, or SS, with safety, PK, and PD assessments at baseline then every 4 weeks for 12 weeks. No dose-limiting toxicities occurred, and all adverse events were grades 1-2, mainly gastrointestinal. Total plasma Se increased after 8 weeks to mean 27.2 μM with SLM, 4.14 μM with MSC and 3.90 μM with SS. No significant changes in DNA damage or intracellular glutathione were observed in peripheral blood mononuclear cells. Mean plasma selenoprotein P (SEPP) increased from 3.74 mg/L at baseline to 4.66 mg/L and 5.13 mg/L after 4 and 8 weeks (p = 0.136 and 0.104, respectively). More detailed evaluations of safety, PK and PD mechanisms are needed to determine a recommended Se compound and dose for larger trials in combination with cancer therapies.

Mefatinib, a novel second-generation epidermal growth factor (EGFR) tyrosine kinase inhibitor that has shown promising antitumor activity in targeting non-small cell lung cancer (NSCLC) with common and uncommon EGFR-activating mutations. In this phase III, randomized, double-blind trial in China, 336 eligible patients with advanced nonsquamous NSCLC harboring EGFR L858R or exon 19 deletion (ex19del) were assigned (2:1) to receive either mefatinib (60 mg daily, n = 223) or gefitinib (250 mg daily, n = 113). The primary endpoint was progression-free survival (PFS), assessed by an independent review committee (IRC). The trial is registered with chinadrugtrials.org.cn (CTR20192297). After a median follow-up of 15.9 months for mefatinib and 18.5 months for gefitinib, mefatinib demonstrated a significantly longer median IRC-assessed PFS compared to gefitinib (13.7 vs. 9.7 months; hazard ratio [HR] = 0.68; 95% confidence intervals [CI]: 0.53-0.87; p = 0.002). The 30-month overall survival rate was 60.2% for mefatinib and 54.3% for gefitinib. Patients with EGFR ex19del had comparable PFS for both treatment arms (p > 0.100), whereas patients with EGFR L858R had significantly longer median PFS when treated with mefatinib than gefitinib (13.7 vs 8.3 months HR = 0.55 [95% CI: 0.38-0.78]; p = 0.001). Patients with EGFR L858R had a 30-month overall survival rate of 56.6% with mefatinib and 43.7% with gefitinib. Treatment-related adverse events ≥grade 3 were reported in 45.7% of the mefatinib group and 24.8% of the gefitinib group. No new safety signals were observed for mefatinib. Mefatinib demonstrated superior efficacy to gefitinib with a similar tolerability profile in the first-line treatment of EGFR-mutated advanced NSCLC.

Brexucabtagene-autoleucel (brexu-cel) is an anti-CD19 chimeric antigen receptor T-cell (CAR-T) product approved for relapsed/refractory Mantle Cell Lymphoma (MCL) after two prior treatment lines, including Bruton tyrosine kinase inhibitors (BTKi). Patients with high-risk (hr) disease-defined by high-intermediate or high-risk MIPI-c, p53 overexpression, or TP53 alterations-have a poor prognosis, underscoring the need for improved first-line strategies. The European Mantle Cell Lymphoma Network therefore designed a phase II trial to investigate the incorporation of brexu-cel into first-line therapy for hr MCL.

Glucuronide prodrug strategies may enhance target specificity and reduce the toxicity of PARP inhibitors, but no clinical evaluation has been performed. We evaluated TSL-1502, a novel glucuronide prodrug of a PARP inhibitor, in a randomized, open-label, phase 2 study at 28 sites in China (NCT05420779). Eligible patients were women aged 18-75 years with HER2-negative locally advanced or metastatic breast cancer and germline BRCA mutations. Patients were assigned randomly (2:2:1) to receive TSL-1502 at 350 mg or 500 mg once daily or the investigator's choice of chemotherapy (eribulin, capecitabine, or vinorelbine) in 3-week cycles. Sixty-three patients were enrolled between August 18, 2022, and March 5, 2024. According to the Independent Review Committee assessment, the objective response rates were 36.0% (95% CI, 18.0-57.5) in the 350 mg group, 55.6% (95% CI, 35.3-74.5) in the 500 mg group, and 40.0% (95% CI, 12.2-73.8) in the chemotherapy group. The median progression-free survival times were 5.6 (95% CI, 4.0-8.2), 8.8 (95% CI, 5.7-not assessable [NA]), and 9.2 (95% CI, 1.38-NA) months, respectively, and the overall survival times were 17.4 months (95% CI, 9.1-NA), not reached (95% CI, 16.9-NA), and 19.8 months (95% CI, 9.2-NA), respectively. Grade ≥3 treatment-related adverse events occurred in 60.0%, 59.3%, and 80.0% of patients, with anemia most common in the TSL-1502 group and neutropenia most common with chemotherapy. No treatment-related deaths occurred. TSL-1502 at 500 mg showed promising antitumor activity and a manageable safety profile, supporting further clinical development.

Postoperative lymph node recurrence in esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis and lacks standardized treatment. Radioresistance and aberrant immune/inflammatory tumor microenvironment (TME) are major barriers limiting the efficacy of concurrent chemoradiotherapy (CRT). This study aimed to evaluate the efficacy, safety, and immune-related radiosensitising mechanisms of anlotinib combined with CRT for postoperative isolated lymph node recurrence of ESCC.

The tumour microenvironment (TME) influences breast cancer progression and treatment response. We investigated whether TME composition predicts tamoxifen benefit in postmenopausal women with oestrogen receptor-positive, HER2-negative (ER+HER2-) breast cancer.

Axillary lymph node dissection (ALND) in breast cancer causes substantial arm morbidity and long-term functional impairment. Less extensive axillary surgery, such as targeted axillary dissection (TAD), significantly reduces this risk. Although omission of ALND is standard in clinically node-negative disease with limited sentinel node involvement, this is not the case for patients with clinically node-positive disease undergoing upfront surgery. The aim of the SENOMAC-ULTRA trial is to evaluate whether TAD can safely replace ALND in patients with clinically node-positive breast cancer receiving upfront surgery.

Dostarlimab in combination with carboplatin-paclitaxel was approved for primary advanced or recurrent endometrial cancer (pA/rEC). The first interim analysis (IA1) of RUBY Part 1 (NCT03981796) showed no significant exposure-response (ER) relationship for progression-free survival or for the five most common dostarlimab-related adverse events (AEs), except rash. Herein, we report the ER relationship between dostarlimab exposure and overall survival (OS) and between dostarlimab exposure and dostarlimab-related AEs. Population pharmacokinetic model was based on IA1, and the predicted exposure metrics from Cycle 1 were used to perform ER analysis at the second interim analysis (IA2). AE analysis was completed for three periods: Cycles 1-6 (chemotherapy phase), Cycle 7 and beyond (monotherapy phase), and all cycles. Included in the OS analysis were 232 patients treated with dostarlimab + carboplatin-paclitaxel. Cox regression of OS showed no significant ER relationship based on dostarlimab Cycle 1 exposure, except for rash and arthralgia. The increase in predicted probabilities for rash and arthralgia for patients with high versus low exposure was limited, ranging from 5.6% to 10.4% for rash and 4.3% to 17.7% for arthralgia (deemed not clinically relevant). These data support the risk/benefit profile at the selected dose of dostarlimab + carboplatin-paclitaxel as standard of care in patients with pA/rEC.

Mature T-cell lymphomas (TCL) are aggressive malignancies with limited effective therapies. Duvelisib (DUV), a dual inhibitor of PI3K-δ and PI3K-γ, has shown promising activity in TCL. Azacitidine (AZA), a hypomethylating agent, has demonstrated efficacy in TCL and may enhance the activity of PI3K inhibitors through epigenetic modulation and immune regulation. We conducted a phase I, open-label, 3 + 3 dose-escalation study of oral duvelisib in combination with oral azacitidine (BMS-986345) in patients with relapsed or refractory TCL. The primary objective was to identify the maximum tolerated dose (MTD) of the combination. Fourteen patients (N = 14) were enrolled with a median age of 63.5 years. The median number of prior therapies was two. Grade ≥ 3 toxicities, expressed for the full treated population (N = 14), included neutropenia (29%), anemia (21%), AST elevation (21%), ALT elevation (14%), thrombocytopenia (14%), and leukocytosis (14%). Most adverse events were grade 1-2 and manageable. The ORR was 46% (N = 6), with 31% (N = 4) complete responses (CR) and 15% (N = 2) partial responses (PR). All four evaluable patients with a T-follicular-helper (TFH) phenotype achieved CR, a hypothesis-generating observation given the small denominator. Median PFS was 2.2 months (95% CI 1.8-NE) and median OS 10.2 months (95% CI 6.3-NE); however, median duration of response was not reached, and three responders were censored at the time of allogeneic transplant. On-treatment suppression of AKT phosphorylation was enhanced during combined therapy. Duvelisib plus oral azacitidine had a manageable safety profile and encouraging activity, particularly in the TFH subtype, where responses were deep and enabled a bridge to allogeneic transplant. Randomized evaluation focused on the TFH subtype is warranted. TRIAL REGISTRATION: NCT05065866.

Modulating tumor-mediated immunosuppression with immunotherapies is an effective therapeutic approach for solid tumors. INCAGN01876 is a humanized IgG1 anti-glucocorticoid-induced tumor necrosis factor receptor (GITR) monoclonal antibody. This phase 1/2 trial evaluated INCAGN01876 plus nivolumab and/or ipilimumab for advanced malignancies.

Neoadjuvant immunotherapy/targeted therapy combined with chemotherapy shows encouraging activity for oropharyngeal squamous cell carcinoma (OPSCC). However, evidence specific to tonsillar squamous cell carcinoma (TSCC) remains limited, particularly regarding the systematic relationships among radiological response, pathologic response, margin control, and voice and swallowing functional outcomes.

Bladder cancer (LABC) after radical cystectomy (RC) is common, even with chemotherapy, and is associated with high morbidity and mortality. Therefore, this work aimed to investigate the effect and efficacy of adjuvant sandwich chemotherapy plus radiotherapy versus adjuvant chemotherapy alone for LABC after RC.

Many older adults with cancer have at least one comorbidity. Type II diabetes mellitus (T2DM) is a common comorbidity among patients with prostate cancer (PC) and represents an important consideration in this population. Comorbid T2DM can negatively impact cancer-specific outcomes for patients, suggesting the need for better glycemic management, especially for patients on active cancer treatment. The goal of this modified Diabetes Self-Management Education Services (mDSMES) pilot study was to provide patients with the opportunity to learn methods of diabetes self-management, including how to manage their glucose levels, improve their understanding and utilization of medication to promote improvements in health, and optimize PC treatment outcomes.

Tumour cells and tumour-associated stroma are key components of the tumour microenvironment, and their interaction impacts disease progression and treatment resistance in rectal cancer. This study introduces a computational approach to quantify tumour cell density (TCD) within epithelial and stromal regions and assess whether treatment response differs according to TCD status in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy (nCRT).

There are few bladder-sparing treatment options for high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer that are effective and have a manageable adverse event profile. Cretostimogene grenadenorepvec (hereafter, cretostimogene) is an oncolytic immunotherapy with dual mechanisms of action-it replicates in and lyses cancer cells with retinoblastoma-E2F pathway alterations and amplifies the immune response. We evaluated the response and safety/tolerability of cretostimogene in patients with high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer.

The SUPREMO trial reported adjuvant chest wall radiotherapy had no effect on 10-year overall survival (primary endpoint) in patients with intermediate-risk breast cancer after mastectomy. The quality of life (QOL) substudy of SUPREMO (UK patients only) examines the effects of chest wall radiotherapy in patients with intermediate-risk breast cancer 1 year, 2 years, 5 years, and 10 years after treatment. Here, we report 5-year QOL results (a secondary endpoint), including prespecified subgroup analyses.

Locally advanced rectal cancer is routinely treated with neoadjuvant radiotherapy. Concomitant systemic anticancer therapy with standard fluoropyrimidines has not generally improved outcomes. Small studies reported high pathological complete response rates and acceptable toxicity using irinotecan and fluoropyrimidine chemoradiation. We aimed to explore the effect of the addition of concomitant irinotecan to standard-of-care chemoradiotherapy in patients with locally advanced rectal cancer.

Ibrutinib has demonstrated inhibition of ErbB/HER tyrosine kinases in preclinical models. This Phase I/II study investigated the safety, efficacy, and immunomodulatory effects of ibrutinib in combination with trastuzumab in patients with HER2-positive metastatic breast cancer (MBC) whose disease had progressed on ado-trastuzumab emtansine therapy. In Phase I, cohorts of three patients received ibrutinib 560 mg or 420 mg by mouth once daily combined with standard dosing of trastuzumab. Phase II enrolled additional patients to assess the primary endpoint of clinical benefit rate (CBR) at 420 mg ibrutinib plus trastuzumab. Flow cytometry and NanoString analyses were performed on peripheral blood mononuclear cells. Overall, 26 patients were enrolled. Patients received a median of three prior regimens containing a HER2-targeted therapy in any setting. The most common treatment-related adverse events were bruising, rash, fatigue, and thrombocytopenia. Four patients (15%) experienced cardiac adverse events, including decreased left ventricular ejection fraction in two patients. The CBR of ibrutinib plus trastuzumab was 19.2% (95% confidence interval: 6.6-39.4). Flow cytometry of T- and natural killer (NK)-cell and myeloid-cell panels showed that treatment statistically significantly decreased T helper 17 (TH17) and myeloid-derived suppressor cells (MDSC) with no decrease in T helper 2 (TH2) cells. Ibrutinib plus trastuzumab was well-tolerated but had limited anti-tumor activity in patients with heavily pretreated, HER2-positive MBC (NCT03379428). Trial Registration: Clinicaltrials.gov, NCT03379428.