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.

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.

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.

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.

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.

TAR-0520 gel is a new topical formulation of brimonidine tartrate designed to prevent chemotherapy-induced skin toxicities. We report here the main outcomes of the phase 1 program which included two double-blind, randomized trials in healthy volunteers (TAR006 and TAR012) and were performed to evaluate the safety, local tolerability, pharmacokinetics, and pharmacodynamics (PD) of TAR-0520 gel.

The TALAPRO-2 trial (NCT03395197) showed that the addition of talazoparib, a potent PARP inhibitor, to enzalutamide significantly improved radiographic progression-free survival in patients with mCRPC. Due to adverse events (AEs), approximately 62% of patients experienced dose interruption and 53% of patients experienced dose reduction of talazoparib in TALAPRO-2 trial. Hematologic AEs such as anemia, thrombocytopenia, and neutropenia were the most common AEs leading to dose interruptions or reductions. We investigated the relationship between talazoparib exposure as well as baseline patients/disease characteristics and Grade ≥ 3 anemia, thrombocytopenia, and neutropenia using graphical examination and Cox proportional hazard models. The results indicated that higher talazoparib exposure, Cavg, t, was associated with a higher risk of Grade ≥ 3 anemia, thrombocytopenia, and neutropenia. Additionally, among the other baseline factors, we observed that higher risk of all tested safety endpoints was associated with lower baseline hemoglobin. In addition, higher risk of anemia was associated with lower baseline body weight and higher baseline lactate dehydrogenase. Higher risk of neutropenia was associated with lower baseline absolute neutrophil count and lower baseline body weight. These findings support the proposed dose modification algorithm as an effective approach for management of AEs.

Chemotherapy-related toxicities often lead to unscheduled health care use and diminished quality of life. Digital health interventions, such as chatbots, offer a scalable solution for supportive care; however, evidence regarding their effectiveness in resource-limited, low- and middle-income settings remains limited.

Preoperative and perioperative nivolumab improve event-free survival in resectable non-small cell lung cancer. The role of adjuvant nivolumab after upfront surgery is unknown.

The phase 1, randomized, open-label, two-way crossover FEEL study assessed the effect of food on the pharmacokinetics of DHP107, an oral paclitaxel with a novel lipid formulation designed to be systemically absorbed without Cremophor EL, in patients with advanced solid tumors.

Patients with colorectal cancer (CRC) undergoing systemic therapy frequently experience functional decline, fatigue, and treatment-related symptoms. Resistance training (RT) is safe during treatment, but the minimum effective duration remains unclear.

Chemotherapy-induced peripheral neuropathy is a frequent side effect of taxane-based chemotherapy, impairing function and quality of life. Exercise is recommended, but comparative effects remain unclear. This study compared whole-body vibration resistance training and conventional aerobic and resistance training in breast cancer survivors with persistent chemotherapy-induced peripheral neuropathy.

Neoadjuvant chemotherapy combined with PD-1 inhibitors has shown application potential in esophageal squamous cell carcinoma (ESCC), however, optimization strategies for administration timing (sequential vs. concurrent) still lack support from prospective evidence.