Bispecific T-cell engagers have revolutionized the treatment and management of hematological malignancies and more recently have started making similar strides for solid tumor indications, with opportunities to become best-in- class therapeutics for cancer. Xaluritamig is a novel bivalent XmAb® 2+1 T cell engager with two STEAP1 binding sites and one CD3 binding site being developed for solid tumors with the primary indication of metastatic castrate resistant prostate cancer (mCRPC). The First-In-Human (FIH) study showed promising anti-tumor activity in mCRPC patients, and the program is currently in late phase clinical development. Xaluritamig was administered as an intravenous infusion once weekly (QW) or once every other week (Q2W) in the dose escalation of the FIH study at dose levels ranging from 0.001 to 2 mg. Initial pharmacokinetic (PK) characterization of xaluritamig exhibited approximately dose-proportional increase in exposures over the dose levels explored, with an estimated terminal half-life of ≈9 days, assuming subjects had no anti-drug antibodies, calculated via the population PK model. The time at which maximum concentration (Cmax) occurred was typically at the end of infusion (median ≈ 1 h), as expected with IV administration. Additionally, thorough dose-exposure-response analyses integrated observed data and model-based simulations of PK, key efficacy endpoints, and safety events to support the evaluation of the target doses 0.75 mg QW, 1.5 mg QW, and 1.5 mg Q2W in dose expansion. This work provides the framework for which modeling and simulations can be used to guide dose selection for dose expansion at an early stage of development adhering to the recent principles of Project Optimus.

The US Food and Drug Administration (FDA) approved trastuzumab deruxtecan (T-DXd, DS-8201a) for patients with unresectable or metastatic breast cancer (MBC) who have tumor progression on previous endocrine therapy (ET) and have hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization [ISH]-) or HER2-ultralow (IHC 0 with membrane staining) tumors.

Belantamab mafodotin (belamaf) combined with standard therapies demonstrated significant progression-free survival (PFS) and overall survival benefits in DREAMM-7 and PFS benefit in DREAMM-8 in relapsed/refractory multiple myeloma. Belamaf dose modifications managed adverse events, including belamaf-related ocular events. Ocular events included ocular adverse reactions (eg, dry eyes, photophobia, eye irritation) and protocol-mandated ophthalmic examination findings. Protocol-recommended dose modifications for ocular events were driven by ophthalmic examination findings and included belamaf dose delays until resolution and reductions. We used descriptive analyses to evaluate the impact of dose modifications on managing ocular events and treatment efficacy. In patients with normal baseline vision who were receiving treatment, dose modifications extended belamaf dosing intervals to a median of 8 to 12 weeks by 9 months; the prevalences of reduced vision to bilateral 20/50 or worse and ocular adverse reactions were highest in the first 3 months and remained low at later time points. The median time to resolution after grade ≥2 ophthalmic examination findings was 12 weeks. Rates of belamaf discontinuations due to ocular events were low. Almost all responders (partial response or better) required dose modifications. Most patients achieved a response before an extended (>2 cycles) dose delay; most who had not, subsequently achieved or deepened their response. In DREAMM-7 and DREAMM-8, the median PFS in patients with ≥1 dose delay of ≥12 weeks was 36.6 months and not reached, respectively. Ocular events were common but effectively managed with dose modifications, allowing for patients to remain on treatment and derive robust efficacy benefit. The trials were registered at www.clinicaltrials.gov as #NCT04246047 (DREAMM-7) and #NCT04484623 (DREAMM-8).

Options remain limited for patients requiring later lines of therapy for metastatic non-small cell lung cancer (mNSCLC) due to poor prognosis and potential toxicities. Therefore, trials of novel combinations of existing therapeutic candidates are warranted. Here, we report robust interim analysis results from the MORPHEUS-Lung study in immune checkpoint inhibitor (CPI)-exposed patients with non-squamous mNSCLC and without targetable gene mutations.

Around 40% of patients undergoing systemic chemotherapy develop oral mucositis (OM), a major cause of morbidity in cancer patients. There are only a few options for preventing and treating OM. This study examines the tolerability of a novel oral device (Bocaliner™), designed to enhance the effects of oral topical therapies, in patients with hematologic malignancies receiving chemotherapy.

Cryotherapy is an effective mucositis intervention for selected chemotherapy regimens, but reliance on ice chips has limited its applicability. Our objective was to assess the efficacy and tolerability of a reusable, self-contained, device as an alternative delivery mode.

Pharmacokinetic boosting can be a strategy to enhance osimertinib exposure and reduce treatment associated costs. The OSIBOOST trial demonstrated that it was feasible to boost low osimertinib plasma trough levels with cobicistat. The current study aims to establish the equivalent dose of cobicistat boosted osimertinib compared to osimertinib 80 mg once daily (QD) by population pharmacokinetic (popPK) modeling. A popPK model was developed on the pharmacokinetic data from the OSIBOOST study using NONMEM 7.4.4. Simulations were performed with cobicistat boosted osimertinib dosing regimens to evaluate their equivalence to the standard of osimertinib 80 mg QD. A dose level was assumed equivalent when the 90% confidence interval (CI) of the geometric mean ratios (GMR) for the area under the curve over 144 h (AUC0-144h) and maximum osimertinib concentration (Cmax) were in the acceptance range of 0.8-1.25. Cobicistat decreased osimertinib CL/F by 29.6% compared to osimertinib monotherapy (P < .0001). Osimertinib 80 mg 2 days on, 1 day off, boosted with cobicistat 150 mg QD was equivalent for osimertinib AUC0-144h (GMR [90% CI] = 0.96 [0.94-0.98]) and Cmax (GMR [90% CI] = 1.06 [1.04-1.08]) compared to osimertinib 80 mg QD monotherapy. However, this regimen was not equivalent for AZ5104 AUC0-144h (GMR [90% CI] = 0.67 [0.66-0.68]) and Cmax (GMR [90% CI] = 0.74 [0.73-0.76]). Theoretically, this reduced dose of cobicistat boosted osimertinib can potentially save approximately 33% in osimertinib treatment associated costs whilst maintaining adequate osimertinib exposure.

Cancer-associated fatigue is a prevalent and distressing symptom in patients receiving palliative chemotherapy. While short-term steroid use has been employed to alleviate fatigue, its long-term efficacy and safety remain unclear.

Chemotherapy-induced nausea and vomiting (CINV) remains a prevalent treatment complication, often significantly impairing patients' quality of life and reducing adherence to chemotherapy regimens. The standard triplet antiemetic regimen, including either a neurokinin-1 (NK1) receptor antagonist (RA) or olanzapine, combined with a 5-hydroxytryptamine type 3 (5-HT3) RA and dexamethasone (DEX), faces challenges primarily due to DEX-related adverse effects and its potential to compromise the efficacy of antitumor agents. This study assessed whether omitting DEX (F-Group: olanzapine + 5-HT3 RA) is non-inferior to the standard D-Group (olanzapine + 5-HT3 RA + DEX). In this multi-center, double-blind, randomized phase III trial, 254 adults with malignant solid tumors (Eastern Cooperative Oncology Group [ECOG] 0-2) scheduled for highly emetogenic chemotherapy (HEC) were randomized 1:1 to the F-Group or D-Group. The primary endpoint was the complete response (CR; no emesis/rescue medication) rate over 0-120 h, with a non-inferiority margin of -15%. Secondary endpoints included CR and complete control (CC; no vomiting/nausea/rescue therapy) rates in acute (0-24 h) and delayed (25-120 h) phases, safety, and quality of life. Overall CR rates were 68.6% (D-Group) and 69.7% (F-Group; p = .9658), demonstrating non-inferiority. Acute phase CR rates were 88.4% versus 86.9% (p = .8643), and delayed phase CR rates were 69.4% versus 69.7% (p > .9999). CC rates were comparable across phases, with no new adverse reactions. The combination of a 5-HT3 RA and olanzapine is as non-inferior as the standard triplet regimen, providing an alternative option for patients receiving HEC. The trial was registered at ClinicalTrials.gov, number NCT05805800.

Cancer immunotherapy with immune checkpoint inhibitors (ICIs) is a pivotal treatment for cancers, including non-small cell lung cancer (NSCLC). ICIs are often associated with adverse events (AEs), including immune-related AEs (irAEs). Bojungikki-tang (BJIKT), a traditional herbal medicine, has immunomodulatory properties and may alleviate fatigue and inflammation in patients with advanced cancer.In this multicenter, randomized, placebo-controlled pilot trial, we evaluated the safety and potential effects of BJIKT on fatigue, muscle loss, and immune response in patients with advanced NSCLC undergoing atezolizumab monotherapy.

To evaluate the feasibility and efficacy of patient-directed behavioral-physical intervention (BPI) for acute hiccups after chemotherapy in cancer patients.

Chemotherapy-induced alopecia (CIA) is a prominent side effect of chemotherapy, negatively impacting the patient's body image and self-confidence. Scalp cooling (SC) has emerged as a preventive option for CIA, but the success rate and adherence vary. Research shows that photobiomodulation (PBM) can improve hair growth by stimulating cell proliferation and repair processes. This trial aims to evaluate the effectiveness of PBM combined with SC in preventing CIA.

Rucaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor with proven efficacy in multiple tumor types. The efficacy of PARP inhibition in endometrial cancer remains unclear.

Chemotherapy- and immunotherapy-induced peripheral neuropathies (PNP) are common and often dose-limiting side effects of cancer treatment. Patients often experience pain, numbness, and tingling in their extremities. Pharmacological options such as duloxetine, which is recommended for chemotherapy-induced PNP (CIPN), offer limited relief [1]. Consequently, neuromuscular training incorporating sensorimotor elements is a promising non-pharmacological alternative. However, its effect on symptoms in the upper extremities remains unexplored. This study investigates the feasibility of combined sensorimotor and vibration training for the upper extremities before and during cancer treatment.

About 15-20% of breast cancers (BC) overexpress Human Epidermal Growth Factor Receptor 2 (HER2+), and 50% of them are also oestrogen receptor positive (ER+). Patients with ER+/HER2+ BC with a limited response to systemic therapies are at an increased risk of relapse, thus understanding the mechanisms of resistance is crucial. This study investigates the changes in gene signature expression (ΔGSE) within ER+/HER2+ tumours and their intrinsic subtype (IS) in response to peri-operative aromatase inhibitors (POAI).

For patients with lentigo maligna who are not suitable for surgery, radiotherapy, or topical imiquimod are alternative nonsurgical treatments.

The metronomic principle of chemotherapy for malignancies, using frequent small doses, has been suggested to show superior efficacy compared with classical administration. Thus, we aimed at investigating whether treatment with Navelbine, according to the metronomic drug schedule, was superior to conventional oral treatment in terms of clinical efficacy and safety. EUDRACT no: 2016-002165-63.

Platelet-rich plasma (PRP) shows potential in treating androgenetic alopecia but lacks evidence for endocrine-induced alopecia (EIA) or persistent chemotherapy-induced alopecia (pCIA).

Hand-foot syndrome (HFS) is the most common adverse effect of capecitabine.

Pranayama breathing exercises may help reduce the burden of chemotherapy-induced symptoms in women with breast cancer. The aim of this study was to determine the effect of pranayama breathing exercise on symptom burden in women with breast cancer undergoing chemotherapy.