https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53837 Wed 28 Feb 2024 15:17:37 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49111 Wed 27 Sep 2023 13:31:53 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54994 Wed 27 Mar 2024 16:38:54 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36361 Wed 24 May 2023 12:19:20 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20549 Wed 11 Apr 2018 09:50:48 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19871 Tue 24 Aug 2021 15:15:16 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42105 PIK3CA-mutant cancer cells. The LORELEI trial tested whether taselisib in combination with letrozole would result in an increased proportion of objective responses and pathological complete responses. Methods: In this multicentre, randomised, double-blind, parallel-cohort, placebo-controlled phase 2, study, we enrolled postmenopausal women (aged ≥18 years) with histologically confirmed, oestrogen receptor (ER)-positive, HER2-negative, stage I–III, operable breast cancer, from 85 hospitals in 22 countries worldwide. To be eligible, patients had have an Eastern Cooperative Oncology Group (ECOG) performance status 0–1, adequate organ function, and had to have evaluable tumour tissue for PIK3CA genotyping. Patients were randomly assigned (1:1) by means of a permuted block algorithm (block size of four) via an interactive voice or web-based response system, to receive letrozole (2·5 mg/day orally, continuously) with either 4 mg of oral taselisib or placebo (on a 5 days-on, 2 days-off schedule) for 16 weeks, followed by surgery. Randomisation was stratified by tumour size and nodal status. Site staff, patients, and the sponsor were masked to treatment assignment. Coprimary endpoints were the proportion of patients who achieved an objective response by centrally assessed breast MRI and a locally assessed pathological complete response in the breast and axilla (ypT0/Tis, ypN0) at surgery in all randomly assigned patients and in patients with PIK3CA-mutant tumours. Analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02273973, and is closed to accrual. Findings: Between Nov 12, 2014, and Aug 12, 2016, 334 participants were enrolled and randomly assigned to receive letrozole and placebo (n=168) or letrozole and taselisib (n=166). Median follow-up was 4·9 months (IQR 4·7–5·1). The study met one of its primary endpoints: the addition of taselisib to letrozole was associated with a higher proportion of patients achieving an objective response in all randomly assigned patients (66 [39%] of 168 patients in the placebo group vs 83 [50%] of 166 in the taselisib group; odds ratio [OR] 1·55, 95% CI 1·00–2·38; p=0·049) and in the PIK3CA-mutant subset (30 [38%] of 79 vs 41 [56%] of 73; OR 2·03, 95% CI 1·06–3·88; p=0·033). No significant differences were observed in pathological complete response between the two groups, either in the overall population (three [2%] of 166 in the taselisib group vs one [1%] of 168 in the placebo group; OR 3·07 [95% CI 0·32–29·85], p=0·37) or in the PIK3CA-mutant cohort (one patient [1%) vs none [0%]; OR not estimable, p=0·48). The most common grade 3–4 adverse events in the taselisib group were gastrointestinal (13 [8%] of 167 patients), infections (eight [5%]), and skin–subcutaneous tissue disorders (eight [5%]). In the placebo group, four (2%) of 167 patients had grade 3 or worse vascular disorders, two (1%) had gastrointestinal disorders, and two (1%) patients had grade 3 or worse infections and infestations. There was no grade 4 hyperglycaemia and grade 3 cases were asymptomatic. Serious adverse events were more common in the taselisib group (eight [5%] patients with infections and seven [4%] with gastrointestinal effects) than in the placebo group (one [1%] patient each with grade 3 postoperative wound and haematoma infection, grade 4 hypertensive encephalopathy, grade 3 acute cardiac failure, and grade 3 breast pain). One death occurred in the taselisib group, which was not considered to be treatment-related. Interpretation: The increase in the proportion of patients who achieved an objective response from the addition of taselisib to endocrine therapy in a neoadjuvant setting is consistent with the clinical benefit observed in hormone receptor-positive, HER2-negative, metastatic breast cancer.]]> Thu 25 Aug 2022 10:26:11 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:47327 Thu 02 May 2024 15:29:57 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11196 Sat 24 Mar 2018 08:13:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:11140 Sat 24 Mar 2018 08:10:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17176 Sat 24 Mar 2018 08:06:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17172 Sat 24 Mar 2018 08:06:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21389 Sat 24 Mar 2018 08:05:04 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:18127 Sat 24 Mar 2018 08:04:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21497 Sat 24 Mar 2018 08:03:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17782 Sat 24 Mar 2018 07:57:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5594 Sat 24 Mar 2018 07:49:21 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:5127 Sat 24 Mar 2018 07:48:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29325 Sat 24 Mar 2018 07:34:20 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:4800 Sat 24 Mar 2018 07:20:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:4697 Sat 24 Mar 2018 07:19:25 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:4862 30 kg/m²) reported more joint symptoms than women with a BMI of 25-30 kg/m² or those with a BMI <25 kg/m² (504 of 1354 women [37·2%] vs 502 of 1926 women [31·3%; OR 1·01 (0·88-1·16)] vs 592 of 1908 women [31·0%; OR 1·32 (1·14-1·53)]) and women on anastrozole reported more joint symptoms compared with those on tamoxifen (949 of 2698 women [35·2%] vs 829 of 2735 women [30·3%]; OR 1·25 [1·11-1·40]). All significant risk factors from the univariate analysis were included in a multivariate analysis and remained significant with little change. Interpretation: In this trial, the major risk factors for developing joint symptoms were previous HRT, hormone-receptor positivity, previous chemotherapy, obesity, and treatment with anastrozole. Discussion of identified risk factors is appropriate when counselling women before initiation of adjuvant hormonal treatment. Funding: This study was funded by Cancer Research UK and AstraZeneca (Macclesfield, UK).]]> Sat 24 Mar 2018 07:18:52 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23364 0.5 ng/mL) alone and when assessed in conjunction with the randomised treatment group increased risk of PCSM in the US trial (PSA nadir p=0.0016; PSA end p=0.017) and Australasian trial (PSA nadir p<0.0001; PSA end p=0.0012). In both trials, the randomised treatment group was no longer associated with PCSM (p>=0.20) when the candidate surrogates were included in the model. Therefore, both PSA metrics satisfied Prentice criteria for surrogacy. INTERPRETATION: After radiotherapy and 6 months of androgen suppression, men with PSA end values exceeding 0.5 ng/mL should be considered for long-term androgen suppression and those with localised or locally advanced prostate cancer with PSA nadir values exceeding 0.5 ng/mL should be considered for inclusion in randomised trials investigating the use of drugs that have extended survival in castration-resistant metastatic prostate cancer.]]> Sat 24 Mar 2018 07:16:30 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54742 Mon 11 Mar 2024 14:26:03 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38069 Fri 12 Nov 2021 12:17:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49118 Fri 05 May 2023 11:46:16 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32124 Fri 04 May 2018 10:39:30 AEST ]]>