Poly (ADP-ribose) polymerase inhibitors (PARPi) exploit DNA repair deficiency in germline BRCA1 and BRCA2 pathogenic variant (gBRCAm) cancers. Haematological toxicity limits chemotherapy-PARPi treatment combinations. In preclinical models we identified a schedule combining olaparib and carboplatin that avoids enhanced toxicity but maintains anti-tumour activity. We investigated this schedule in a neoadjuvant, phase II-III, randomised controlled trial for gBRCAm breast cancers (ClinicalTrials.gov ID:NCT03150576; PARTNER). The research arm included carboplatin (Area Under the Curve 5, 3-weekly); paclitaxel (80 mg/m2, weekly) day 1, plus olaparib (150 mg twice daily) day 3-14 (4 cycles), followed by anthracycline-containing chemotherapy (3 cycles); control arm gave chemotherapy alone. The primary endpoint, pathological complete response rate, showed no statistical difference between research 64.1% (25/39); control 69.8% (30/43) (p = 0.59). However, estimated survival outcomes at 36-months demonstrated improved event-free survival: research 96.4%, control 80.1% (p = 0.04); overall survival: research 100%, control 88.2% (p = 0.04) and breast cancer specific survival: research 100%, control 88.2% (p = 0.04). There were no statistical differences in relapse-free survival and distant disease-free survival, both were: research 96.4%, control 87.9% (p = 0.20). Similarly, local recurrence-free survival and time to second cancer were both: research 96.4%, control 87.8% (p = 0.20). The PARTNER trial identified a safe, tolerable schedule combining neoadjuvant chemotherapy with olaparib. This combination demonstrated schedule-dependent overall survival benefit in early-stage gBRCAm breast cancer. This result needs confirmation in larger trials.

In the phase 3 EMPOWER-Lung 1 study, first-line cemiplimab monotherapy provided significant survival benefit versus chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. This exploratory subgroup analysis investigated the clinical outcomes of cemiplimab treatment in patients with advanced NSCLC with brain metastases.

Initial results of this study, reported after a median follow-up close to 4 years, demonstrated improved time to initiation of new treatment (TTNT) for patients with advanced stage, asymptomatic, low tumour burden follicular lymphoma who received early rituximab monotherapy when compared with watchful waiting. Given the long natural history of follicular lymphoma, the trial was extended to further assess TTNT with longer follow-up. Mature data are presented here.

In the phase 3 ponatinib-3001 trial (PhALLCON, NCT03589326), ponatinib demonstrated superior efficacy over imatinib with comparable safety in patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). This post hoc analysis evaluated the net benefits of ponatinib using a quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) approach.

The current standard treatment for chemotherapy-induced nausea and vomiting (CINV) with standard antiemetics is insufficient. Rikkunshito, a Japanese traditional herbal medicine, has been shown to improve cisplatin-induced anorexia and functional dyspepsia, and our exploratory study found that rikkunshito has an additive beneficial effect on CINV in patients with uterine corpus and cervical cancer receiving cisplatin containing chemotherapy (JORTC KMP-02).

The purpose of digital remote monitoring (DRM) is improving cancer care management. However, its effectiveness largely depends on the role of nurse navigators (NNs) within these systems to process data and lead action.

The potential benefit of adding photodynamic therapy (PDT) to intravitreal aflibercept injection (IAI) in eyes with polypoidal choroidal vasculopathy (PCV) remains unclear.

In the phase 3 CheckMate 76 K trial, adjuvant nivolumab significantly improved recurrence-free survival and distant metastasis-free survival versus placebo in patients with resected stage IIB/C melanoma. We report patient-reported outcomes from CheckMate 76 K.

We leverage a clinical trial (NCT04080804) that compared neoadjuvant anti-PD-1, anti-PD-1+CTLA-4, and anti-PD-1+LAG-3 therapies in head and neck squamous cell carcinoma patients. Combination therapies promote higher pathologic response rates versus monotherapy, and major pathologic response is associated with better survival. To address whether successful immune checkpoint inhibitor (ICI) regimens act through similar or distinct pathways, we robustly and longitudinally characterize transcriptional and proteomic dynamics of CD8+ tumor-infiltrating lymphocytes (TILs) in a clonal manner. Anti-PD-1+LAG-3 reprograms CD8+ TIL with type-I interferon response and exhaustion gene programs into effector memory and resident memory (TEM/TRM). In contrast, anti-PD-1+CTLA-4 activates and expands pre-existing TEM/TRM CD8+ TIL, but does not rejuvenate exhausted phenotypes into T effector cells. Anti-PD-1+LAG-3, but not anti-PD-1+CTLA-4, induces widespread TCR sharing among the different transcriptional states, as well as increased TCR diversity in responding patients. Our data suggest doublet regimen-specific transcriptional and clonal dynamics of tumor-reactive CD8+ T cells.

Frequent visits and intravitreal anti-vascular endothelial growth factor (VEGF) injections are often required to manage diabetic macular edema (DME), burdening patients and their health care networks. The Port Delivery System (PDS) with ranibizumab is the first continuous anti-VEGF therapy that has the potential to reduce visit and treatment burden without sacrificing vision outcomes for patients with DME.

Frequent prophylactic intravitreal anti-vascular endothelial growth factor injections can reduce risk of progression to vision-threatening complications in nonproliferative diabetic retinopathy (NPDR). A refillable drug delivery system for continuous intraocular ranibizumab release could offer less frequent treatment regimens.

Bevacizumab shows inter-individual pharmacokinetic variability, with an exposure-response relationship in metastatic colorectal cancer (mCRC) patients. This study explores whether a double dose of bevacizumab, compared to a standard dose, increases efficacy in mCRC patients treated with bevacizumab-based chemotherapy as first-line therapy and who have a low initial trough concentration of bevacizumab. PHARBEVACOL is a multicenter, randomized, double-blind, two-parallel group trial. All patients will receive first-line bi-weekly 5 mg/kg bevacizumab-based chemotherapy and those with low initial bevacizumab concentrations (≤15.5 mg/L) will be randomized to either continue the standard dose (5 mg/kg every 14 days) or receive a double dose (10 mg/kg every 14 days). The primary objective is to evaluate the effect of doubling dose on progression-free survival (PFS). During a screening phase, the first serum trough concentration will be measured on day 14, before the second infusion of bevacizumab. We hypothesize a 40 % PFS in the control group at 9 months versus 60 % in the study group, corresponding to a hazard ratio of 0.56. With 80 % power, a 5 % two-sided type I error, and a minimum 12-month follow-up, 116 patients need to be included. Since only 50 % of screened patients will be eligible for randomization, approximately 244 patients will be screened. Recruitment is scheduled to begin in February 2025.

Many chemotherapy agents used to treat advanced cancer are inherently mucotoxic, causing breakdown of the gastrointestinal mucosa (gastrointestinal mucositis (GI-M)) and lead to a constellation of secondary complications including diarrhoea, malnutrition, anorexia, pain, fatigue and sleep disturbances. These symptoms are usually managed individually, leading to polypharmacy and its associated risks. The endocannabinoid system regulates numerous biological and behavioural processes associated with chemotherapy side effects, suggesting its modulation could control these symptoms. Therefore, the CANnabinoids in CANcer (CANCAN) therapy trial is a phase II, randomised, double-blind, placebo-controlled trial that aims to determine the efficacy of medicinal cannabis in minimising GI-M and its associated symptom burden.

Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 inhibitors, have demonstrated significant survival benefits in treating recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). While baseline peripheral blood lymphocyte subsets have been identified as prognostic biomarkers in various cancers treated with ICIs, their relevance in R/M-NPC has not been extensively studied.

To estimate in humans, in vivo, drug retention in the subretinal space following either 1- or 2-step subretinal injection (SRI).

Peripheral neuropathy is a major adverse effect of Vincristine (VCR) in pediatric acute lymphoblastic leukemia (ALL) patients. Curcumin can prevent the development of many neurological diseases.

The purpose of this study was to evaluate the angiographic predictors of response to the anti-vascular endothelial growth factor-C/-D agent, sozinibercept.

Hand-foot syndrome (HFS) is a common adverse event of capecitabine causing treatment modifications. Topical urea cream can reduce sorafenib-induced hand-foot skin reaction. However, its benefit in preventing capecitabine-associated HFS was not seen early in the course and had been unknown with long-term use. The aim of this study was to evaluate the efficacy of urea cream for HFS prophylaxis throughout capecitabine treatment.

Equivalence between HLX02 and trastuzumab sourced from the European Union (EU-trastuzumab), in combination with docetaxel, was demonstrated in a phase III study. This study aimed to evaluate the long-term efficacy and safety data after 3 years of follow-up.

Data on exposure-response or exposure-toxicity relationships of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are limited and inconclusive. We aimed to investigate whether there is an association between palbociclib exposure and progression-free survival (PFS), adverse events (AEs) and dose reductions.