Population pharmacokinetic (PK) and exposure-response analyses were performed to characterize the PK and exposure-response relationships of vepdegestrant, a first-in-class, oral PROteolysis-TArgeting Chimera estrogen receptor degrader. Population PK and exposure-response analyses for safety utilized data from the first-in-human study (ARV-471-mBC-101, NCT04072952) and the registrational VERITAC-2 study (NCT05654623), which included patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Safety endpoints of clinical interest were evaluated using logistic regression and included grade ≥3 treatment-emergent adverse events (TEAEs) and TEAEs of any grade (arthralgia, fatigue, nausea, aspartate aminotransferase or alanine aminotransferase elevations, anemia, and neutrophil count decreased). Exposure-efficacy analysis included patients with estrogen receptor-1 (ESR1)-mutated, ER-positive, HER2-negative advanced breast cancer from the VERITAC-2 vepdegestrant arm only. Progression-free survival (PFS) as assessed by blinded independent central review, the primary efficacy endpoint in VERITAC-2, was assessed via Cox proportional hazards modeling. Vepdegestrant PK was described by a two-compartment model with linear elimination and sequential zero-, first-order absorption. None of the evaluated covariates significantly influenced the disposition of vepdegestrant. There was no statistically significant relationship between vepdegestrant exposure and any of the evaluated safety endpoints across 30-500 mg total daily doses. In patients with ESR1-mutated, ER-positive, HER2-negative advanced breast cancer treated with vepdegestrant 200 mg once daily in the VERITAC-2 study, exposure was not a statistically significant predictor of PFS. Overall, integrated analyses adequately characterized the PK of vepdegestrant, with no clinically meaningful covariate effects. No exposure-response relationships were identified between vepdegestrant exposure and efficacy or safety outcomes.

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.

Taxane-induced peripheral neuropathy (TIPN) is a common side effect of chemotherapy that significantly impacts patients' quality of life. This study evaluated the efficacy of professional acupuncture and self-care using press-tack needles for TIPN.

The primary objective of this study was to evaluate the efficacy of oral nutritional supplements (ONS) on chemotherapy tolerance and long-term survival outcomes in postoperative colorectal cancer patients undergoing chemotherapy.

This study aimed to develop a dynamic-static combined Neiyanggong intervention for breast cancer patients undergoing chemotherapy and to evaluate its effectiveness in alleviating cancer-related fatigue, with sleep quality assessed as a secondary outcome.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect that leads to sensory deficits, impaired balance, and a reduced quality of life (QoL). This study evaluates the effectiveness of sensorimotor and balance training compared with conventional physiotherapy.

Non-Hodgkin's lymphoma (NHL) is a diverse group of lymphoproliferative malignancies that predominantly affects older adults. Chemotherapy remains the primary modality of treatment for many NHL subtypes, yet it often brings about adverse effects such as myelosuppression, anemia, and neuropathy, all of which contribute to a heightened risk of falls in older patients. Falls in this population can lead to serious complications, including fractures and intracranial injuries, thereby impacting functional status and potentially delaying oncological treatment.

Oxaliplatin-induced peripheral neuropathy (OIPN) affects up to 80% of patients receiving oxaliplatin-based chemotherapy, and effective preventive strategies remain limited. Huangqi Guizhi Wuwu Decoction (HQGZWWD), a traditional Chinese herbal formula included in China's National Classic Famous Formulas, is widely used for OIPN in clinical practice, but high-quality clinical evidence remains lacking.

This study aimed to determine the effect of listening to music during chemotherapy sessions on depression, anxiety, stress, and treatment-related symptoms.

Anaplastic lymphoma kinase (ALK) inhibitors have emerged as promising agents for patients with resectable ALK-positive non-small-cell lung cancer (NSCLC). Whether ensartinib, a second-generation ALK inhibitor, is safe and effective in such patients is unknown.

Chemotherapy-induced diarrhea (CID) and constipation (CIC) are prevalent, distressing symptoms that can adversely affect nutritional status and treatment tolerance. Evidence for non-pharmacological management remains limited, particularly in low-resource settings. This pilot randomized study assessed feasibility, acceptability, and preliminary effectiveness of a co-designed, nurse-led nutritional support program for managing CID and CIC in patients with cancer in Vietnam.

Paclitaxel is an effective chemotherapeutic agent for breast cancer, but its use is often limited by cumulative toxicities linked to mitochondrial dysfunction and oxidative stress. This study investigated whether Coenzyme Q10 (CoQ10) could mitigate paclitaxel-induced adverse events and improve treatment tolerability.

Dostarlimab+carboplatin-paclitaxel followed by dostarlimab maintenance demonstrated statistically significant and clinically meaningful benefits in progression-free and overall survival in the overall population of primary advanced/recurrent endometrial cancer versus chemotherapy alone in Part 1 of the phase 3 ENGOT-EN6-NSGO/GOG-3031/RUBY trial (NCT03981796). Part 2 evaluated the efficacy and safety of the addition of the poly(adenosine diphosphate-ribose) polymerase inhibitor niraparib to dostarlimab maintenance following dostarlimab+chemotherapy versus placebo maintenance following placebo+chemotherapy in primary advanced/recurrent endometrial cancer.

To report updated patient-reported (PRO) health-related quality of life (HRQOL) findings and evaluate the effect of disease progression on HRQOL using data from the final analysis of the PRIMA/ENGOT-OV26/GOG-3012 trial.

Adjuvant pembrolizumab improves disease-free and overall survival among patients with resected clear-cell renal-cell carcinoma. The hypoxia-inducible factor 2α inhibitor belzutifan has activity in advanced disease. Adjuvant pembrolizumab with belzutifan may further improve outcomes in patients with clear-cell renal-cell carcinoma at increased risk for recurrence.

Here we report long-term outcomes of adjuvant metronomic capecitabine in patients with locoregionally advanced nasopharyngeal carcinoma. In this multicenter, open-label, parallel-group, randomized, controlled, phase 3 trial, 406 patients who had completed definitive chemoradiotherapy were randomly assigned (1:1) to receive either adjuvant metronomic capecitabine (650 mg m-2 twice daily for 1 year) or observation. The primary endpoint was failure-free survival; secondary endpoints included overall survival (OS), distant failure-free survival, locoregional failure-free survival, and safety, as reported in this analysis. The trial met its primary endpoint. With a median follow-up of 71.3 months, metronomic capecitabine significantly improved OS (hazard ratio = 0.53, 95% confidence interval, 0.31-0.91, P = 0.019). Grade 3 adverse events occurred in 35 (17%) of 201 patients in the metronomic capecitabine group and 11 (6%) of 200 in the observation group; one (<1%) grade 4 neutropenia was reported. In a post hoc analysis, completion of the 1 year course was associated with improved OS, whereas dose reductions and relative dose intensity showed no association with OS. Patients with a higher post-radiotherapy neutrophil-to-lymphocyte ratio derived greater benefit from metronomic capecitabine. These findings support the long-term therapeutic benefit of adjuvant metronomic capecitabine in locoregionally advanced nasopharyngeal carcinoma. ClinicalTrials.gov identifier: NCT02958111 .

Background: SYHX2011 is a novel albumin-bound paclitaxel, in which most nonparticulate human albumin is replaced with mannitol and sucrose. This study aimed to compare SYHX2011 and paclitaxel for injection (albumin-bound) (PAB) in patients with breast cancer. Methods: Patients with histologically or cytologically confirmed unresectable locally advanced or metastatic breast cancer were randomly assigned to receive SYHX2011 (260 mg/m2) or PAB (260 mg/m2) intravenously once every 3 weeks, stratified by prior taxane use and rash history (prior taxane with rash, prior taxane without rash, or no prior taxane), as well prior lines of chemotherapy for advanced disease (0 or ≥1). The primary endpoint was objective response rate assessed by an independent review committee. Noninferiority was to be declared if the lower bound of the 95% confidence interval (CI) for the rate ratio exceeded 0.75; if the lower bound exceeded 1, superiority would subsequently be tested and considered confirmed. Results: In this multicenter, randomized, double-blind, phase III trial across 56 centers in China, 621 patients were screened between 2023 April 23 and 2024 March 21, of whom 459 patients were randomized to SYHX2011 (n = 229) or PAB (n = 230). The confirmed objective response rate assessed by an independent review committee was 35.8% (95% CI 29.4% to 42.6%) for SYHX2011 and 25.8% (95% CI 20.2% to 32.1%) for PAB (rate ratio = 1.38, 95% CI 1.04 to 1.84; one-sided P = 0.012), indicating that SYHX2011 was noninferior to PAB. The superiority of SYHX2011 over PAB was also confirmed. SYHX2011 showed a lower incidence of rash compared with PAB during the first 2 administration cycles (13.6% vs. 34.3%) and all treatment cycles (16.2% vs. 42.6%). Treatment-related adverse events (TRAEs) occurred in 98.2% of patients receiving SYHX2011 and 98.3% of patients receiving PAB. In the SYHX2011 group, 111 (48.7%) patients experienced grade ≥3 TRAEs, compared with 101 (43.9%) patients in the PAB group. The most common grade ≥3 TRAEs were neutropenia, leukopenia, and peripheral sensory neuropathy. The median investigational drug reconstitution time was 2.0 min for SYHX2011 and 11.0 min for PAB. Conclusions: SYHX2011 demonstrated greater therapeutic benefits than PAB and significantly reduced the incidence of rash. Additionally, it could offer greater convenience in clinical application, providing advanced breast cancer patients with more effective and safer treatment options. Trial registration: ClinicalTrials.gov identifier: NCT05753865. Date of registration: 2023 February 22.

ASC4FIRST (ClinicalTrials.gov NCT04971226) is a pivotal phase 3 clinical trial comparing the efficacy and safety of asciminib vs. standard of care (SoC) tyrosine kinase inhibitors (TKIs) in newly diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP). The study demonstrated superior efficacy and a favorable safety profile for asciminib vs. all current SoC TKIs; this subgroup analysis involved 138 patients from East Asian sites enrolled in ASC4FIRST. Patients were randomized to receive either asciminib or investigator-selected TKIs (IS-TKIs: imatinib, bosutinib, dasatinib, or nilotinib) following stratification by risk category and prerandomization-selected TKI (imatinib or second-generation TKI). Consistent with non-East Asian patients, asciminib showed better efficacy in East Asian patients, with a major molecular response (MMR) rate at Week 48 and Week 96 of 64.9% and 77.0% compared to 45.3% and 57.8% for all IS-TKIs combined, respectively (common treatment difference: 19.5% and 20.0%, respectively). Similar results were obtained for patients with imatinib as the prerandomization-selected TKI (MMR rate at Week 48 and Week 96: 67.9% and 78.6% for asciminib compared to 30.8% and 46.2% for imatinib, respectively; common treatment difference: 36.5% and 32.7%, respectively). Asciminib also showed a favorable safety profile in East Asian patients, with lower rates of Grade ≥ 3 adverse events (AEs) and AEs leading to discontinuation compared to IS-TKIs (41.9% vs. 54.0% and 2.7% vs. 9.5%, respectively), consistent with the results from non-East Asian patients. These findings support the use of asciminib as a first-line treatment option for East Asian and non-East Asian patients with CML-CP.

Although tislelizumab is approved across multiple malignancies and dosing schedules, intravenous administration imposes logistical burdens. A subcutaneous formulation may improve convenience and reduce resource demands if comparable exposure is achieved. This study evaluated the pharmacokinetics, bioavailability, and injection-site performance of subcutaneous tislelizumab and used population pharmacokinetic (PopPK) modeling and simulations to support phase 3 dose selection. In the phase 1 BGB-A317-103 study, treatment-naïve patients with locally advanced or metastatic non-small cell lung cancer received tislelizumab via subcutaneous thigh, subcutaneous abdominal, or intravenous administration. A PopPK model was developed with subcutaneous compartments to characterize site-specific absorption and covariate effects. Simulations compared subcutaneous 300 mg every 3 weeks (Q3W) with intravenous 200 mg Q3W regimens to estimate the probability of achieving comparable pharmacokinetic exposure. The PopPK model demonstrated greater bioavailability and lower variability with subcutaneous thigh vs. abdominal administration. Estimated absorption rates were 0.189 1/d for thigh and 0.247 1/d for abdomen, with corresponding bioavailability estimates of 86.6% and 73.1%. The model described absorption and exposure across administration routes and supported the simulation of 1,000 trials. Subcutaneous 300 mg thigh administration achieved pharmacokinetic exposures comparable to intravenous 200 mg across key parameters, including trough concentration and area under the curve (AUC) at Cycle 1 and steady state, whereas abdominal administration showed reduced probability of achieving target exposure thresholds for Cycle 1 AUC. Tislelizumab 300 mg Q3W subcutaneous thigh administration is predicted to provide exposure comparable to intravenous 200 mg Q3W, supporting its selection for phase 3 evaluation. Trial registration: ClinicalTrials.gov identifier: NCT06091943.

Since hand-foot skin reaction (HFSR) is a dose-limiting toxicity associated with certain multikinase inhibitors, prophylactic measures to manage this adverse effect require improvement. This study aimed to evaluate the efficacy of depressurization using hydrocolloid dressing by comparing the effects of adding hydrocolloid dressing to standard prophylactic moisturizing versus moisturizing alone.