Sir Charles Gairdner Hospital (SCGH) is a teaching hospital in Nedlands, Western Australia.Opened in 1958 as the Perth Chest Hospital and later named in honour of Sir Charles Gairdner, governor of Western Australia from 1951 to 1963, it is part of the Queen Elizabeth II Medical Centre (QEII MC). It is colloquially referred to as "Charlie's".All clinical specialities are provided, with the exception of complex burns, paediatrics, obstetrics, gynaecology and major trauma. It houses the state's only comprehensive cancer treatment centre, and is the state's principal hospital for neurosurgery and liver transplants. The hospital is closely associated with the nearby University of Western Australia as well as Curtin University, Notre Dame University, and Edith Cowan University.Handling over 76,000 admissions annually, SCGH has 600 beds, and treats approximately 420,000 patients each year. As of 2012[update] some 5,500 staff are employed. In 2009, it was the second hospital in Australia to be awarded Magnet recognition by the American Nurses Credentialing Center.
Metastatic disease is a common occurrence in malignancy with certain cancers recognised to have a high incidence of metastases, particularly the liver, lungs, and bones. Tumour-to-tumour metastases are an exceptionally rare occurrence, where a distant malignancy metastasises to a secondary distinct tumour. Breast and lung carcinomas are the more commonly reported origin sites, whilst renal cell carcinomas and meningiomas are the most reported recipient malignant and benign tumours respectively. In this article, we describe an unusual case of a metastatic head and neck squamous cell carcinoma (HNSCC) complicated by tumour-to-tumour metastasis to a benign intramedullary cartilage lesion in the distal femur.
Abstract Introduction: Covalent Bruton tyrosine kinase inhibitors (cBTKi) are a mainstay of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) treatment. Pirtobrutinib is a highly selective, non-covalent BTKi with proven efficacy in CLL/SLL patients (pts) previously treated with a cBTKi. We report results from the first head-to-head comparison of pirtobrutinib versus ibrutinib in treatment-naïve (TN) pts and pts with cBTKi-naive relapsed/refractory (R/R) CLL/SLL (NCT05254743). Methods: Eligible pts were randomized 1:1 to receive pirtobrutinib (200 mg QD) or ibrutinib (420 mg QD), stratified by del(17p) status and number of prior lines of therapy (0 vs 1 vs ≥ 2). Treatment was administered until progression or development of unacceptable toxicity. Primary endpoints were non-inferiority (NI) of overall response rate (ORR; partial response or better by independent review committee [IRC]/iwCLL 2018), in intent-to-treat (ITT) and R/R populations, with ORR ratio NI margins of 0.88 and 0.86, respectively. PFS was a secondary endpoint to be tested for superiority at a future timepoint. We present the final ORR analyses in ITT and R/R populations, and descriptive analyses of secondary endpoints, including in the TN population, using a 10June2025 data cut. Results: From 18August2022 to 17June2024, 662 pts were randomized to receive pirtobrutinib (n=331) or ibrutinib (n=331). For both arms, the median age was 67 (pirtobrutinib range, 39-90; ibrutinib, 34-86), and the median number of prior therapies was 1. The ITT population included 225 TN and 437 R/R pts. Among pirtobrutinib vs ibrutinib pts with evaluable samples, unmutated IGHV was 68% (199/293) vs 66% (183/277), complex karyotype ≥3 abnormalities was 40% (104/259) vs 34% (78/227), and del(17p) was 15% (50/331) vs 16% (52/331), respectively. The study met its primary endpoint demonstrating statistically significant NI of ORR of pirtobrutinib vs ibrutinib in both the ITT population (87.0% [95%CI,82.9-90.4] vs 78.6% [95%CI,73.7-82.9]; ORR ratio=1.11 [95%CI,1.03-1.19]; 2-sided p<0.0001) and R/R population (84.0% [95%CI,78.5-88.6] vs 74.8% [95%CI,68.5-80.4]; ORR ratio=1.12 [95%CI,1.02-1.24]; 2-sided p<0.0001), respectively. In the TN population, ORR was 92.9% (95%CI,86.4-96.9) with pirtobrutinib vs 85.8% (95%CI,78.0-91.7) with ibrutinib. ORR consistently favored pirtobrutinib vs ibrutinib across subgroups in both the ITT and R/R population, including del(17p) (ITT, 80.0% vs 75.0%; R/R, 80.6% vs 80.0%) and without del(17p) (ITT, 88.3% vs 79.2%; R/R, 84.7% vs 73.8%). PFS data were not yet mature, but favored pirtobrutinib in ITT (HR, 0.57 [95%CI,0.39-0.83]), R/R (HR, 0.73 [95%CI,0.47-1.13]), and TN (HR, 0.24 [95%CI,0.10-0.59]) pts, with a median follow up of 21.8 months, 18.2 months, and 22.5 months, respectively. The 18-month PFS rates (95%CI) in pirtobrutinib and ibrutinib arms were86.9% (82.4-90.3) vs 82.3% (77.3-86.3) in ITT, 81.7% (75.1-86.7) vs 79.2% (72.3-84.6) in R/R, and 95.3% (89.1-98.0) vs 87.6% (79.7-92.6) in TN, respectively. There was no detriment in overall survival (HR, 0.961 [95%CI,0.55-1.69]) for the ITT population. The most common treatment-emergent adverse events were similar between arms. Adverse events (AE) of interest, such as atrial fibrillation/flutter occurred in 2.4% of pirtobrutinib and 13.5% of ibrutinib pts; hypertension in 10.6% and 15.1% of pts, respectively. Fewer AE-related dose reductions were seen with pirtobrutinib (7.9%) vs ibrutinib (18.2%). Treatment discontinuation due to progressive disease was more common with ibrutinib (pirtobrutinib, n=15 [4.5%] vs ibrutinib, n=36 [10.9%]), and similar for AE (pirtobrutinib, n=26 [7.9%] vs ibrutinib, n=24 [7.3%]). Treatment is ongoing in 81.3% of pirtobrutinib and 69.5% of ibrutinib pts. Conclusion:In this first head-to-head study, in cBTKi-naïve CLL/SLL, including pts with treatment naïve CLL, pirtobrutinib demonstrated NI of ORR vs ibrutinib in both ITT and R/R populations. PFS, while not yet mature, trended in favor of pirtobrutinib, with the most pronounced effect in the TN population, which had the longest follow-up at this data cut.
BACKGROUND:The efficacy of teclistamab, a bispecific antibody targeting B-cell maturation antigen and CD3, as early-line monotherapy in relapsed or refractory multiple myeloma is unclear. METHODS:We randomly assigned patients with relapsed or refractory multiple myeloma who had previously received one, two, or three lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide, to receive teclistamab or the investigator's choice of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd). Antimicrobial prophylaxis and immune globulin replacement were recommended. The primary end point was progression-free survival as assessed by an independent review committee. RESULTS:A total of 296 patients were assigned to teclistamab and 297 to PVd or Kd. At the interim analysis (median follow-up, 17.3 months), teclistamab significantly improved progression-free survival as compared with PVd or Kd (estimated 18-month progression-free survival, 69.8% vs. 26.9%; hazard ratio for disease progression or death, 0.29; 95% confidence interval [CI], 0.23 to 0.38; P<0.001). The percentage of patients with a complete response or better was higher with teclistamab than with PVd or Kd (65.9% vs. 16.8%, P<0.001). Overall survival was improved with teclistamab as compared with PVd or Kd (estimated 18-month overall survival, 79.2% vs. 68.6%; hazard ratio for death, 0.60; 95% CI, 0.43 to 0.83; P = 0.002). Adverse events of grade 3 or 4 occurred in 84.9% of teclistamab recipients and in 76.3% of PVd or Kd recipients, with grade 5 adverse events in 6.5% and 3.5%, respectively. Cytokine release syndrome, mostly of grade 1 or 2, occurred in 66.0% of teclistamab recipients, and immune effector cell-associated neurotoxicity syndrome occurred in 4.1%. Grade 3 or 4 infection occurred in 41.6% of teclistamab recipients and in 29.0% of PVd or Kd recipients. CONCLUSIONS:Among patients with multiple myeloma and one to three previous lines of therapy, teclistamab significantly improved progression-free and overall survival as compared with PVd or Kd. Infections of grade 3 or 4 were common. (Funded by Johnson & Johnson; MajesTEC-9 ClinicalTrials.gov number, NCT05572515.).
ABSTRACT:Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who harbor del(17p) and/or tumor protein p53 (TP53) mutations represent a high-risk population with a historically poor prognosis. To assess zanubrutinib efficacy and safety outcomes in patients with CLL/SLL with del(17p) and/or TP53 mutations (N = 301; n = 132, treatment-naive [TN]; n = 169, relapsed/refractory [R/R]), data from SEQUOIA (phase 3; TN; zanubrutinib; NCT03336333), ALPINE (phase 3; R/R; zanubrutinib vs ibrutinib; NCT03734016), and AU-003 (NCT02343120) (phase 1/2; zanubrutinib) were evaluated. In SEQUOIA (n = 127; median follow-up, 64.8 months), median progression-free survival (PFS) and overall survival (OS) were not reached; estimated 60-month PFS and OS were 70.7% and 82.3%, respectively. In ALPINE (n = 75, each treatment arm; median follow-up, 39.0 months), 36-month PFS rates were 59.2% among patients treated with zanubrutinib and 38.5% among those treated with ibrutinib, and OS rates were 73.6% and 72.5%, respectively. In AU-003 (n = 24; median follow-up, 69.6 months), 10 of 24 patients experienced progressive disease. Rate of response with zanubrutinib in SEQUOIA was 96.9% (95% confidence interval [CI], 95.2-98.8), and in ALPINE was 89.3% (95% CI, 80.1-95.3) with zanubrutinib vs 76.0% (95% CI, 64.7-85.1) with ibrutinib. Responses deepened over time in both TN and R/R populations. The most frequent nonhematologic treatment-emergent adverse events occurring in >20% of patients treated with zanubrutinib with del(17p) and/or TP53 mutations in SEQUOIA and ALPINE were COVID-19, upper respiratory tract infection, arthralgia, diarrhea, and contusion. In conclusion, zanubrutinib demonstrated strong efficacy in high-risk del(17p) and/or TP53 CLL/SLL, with a tolerable safety profile, further supporting use of zanubrutinib in both frontline and R/R settings.
INTRODUCTION:Older people face higher risks of medicine-related harm due to polypharmacy and the use of potentially inappropriate medicines. Current treatment guidelines rarely specify when to stop medicines, leading to medicines often being continued indefinitely without a clear deprescribing plan. While deprescribing guidelines exist for some medicine classes, limited guidance is a major barrier to deprescribing. These new guidelines address this gap by providing structured recommendations that complement more detailed drug-specific deprescribing guidance, disease-specific therapeutic guidelines and non-pharmacological management resources. These guidelines were developed by a team of 72 experts, including consumer representatives, and were further shaped by feedback from public consultation and independent reviewers. MAIN RECOMMENDATIONS:The guidelines are intended for all healthcare professionals involved in prescribing, dispensing or administering medicines to older people. The guidelines specifically address polypharmacy and medicines commonly dispensed for regular use in people aged ≥ 65 years, as well as other medicines where there is evidence to consider deprescribing in this cohort. The guidelines provide 185 consensus-based recommendations and 70 good practice statements, covering both specific medicine categories and general deprescribing principles. The guidelines are structured into four areas: (1) when to deprescribe; (2) ongoing treatment needs; (3) how to deprescribe; and (4) monitoring requirements. CHANGES IN CARE AS A RESULT OF THE GUIDELINE:This guideline emphasises deprescribing as an integral part of the prescribing continuum. Applying a deprescribing approach encourages prescribers to consider the ongoing need for a medicine each time a prescription is re-issued, to balance benefits and harms as they evolve over time, and to ensure treatment decisions reflect an individual's goals through shared decision-making. The guideline was developed based on currently available evidence for deprescribing and expert multidisciplinary and consumer input. It supports health professionals in reviewing regular medicines, minimising harm and planning ongoing treatment or monitoring. The detailed guideline is available at https://deprescribing.com.
