https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50456 2 cm (4.5%) or grade 3 tumors (5.5%). These sustained reductions of the risk of recurrence with adjuvant exemestane + OFS, compared with tamoxifen + OFS, provide guidance for selecting patients for whom exemestane should be preferred over tamoxifen in the setting of OFS.]]> Wed 28 Feb 2024 15:10:42 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18998 Wed 20 May 2020 07:08:07 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22946 Wed 11 Apr 2018 16:42:13 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14183 Wed 11 Apr 2018 13:18:25 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:16287 Wed 11 Apr 2018 11:53:01 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22889 Annals of Oncology online.]]> Wed 11 Apr 2018 11:24:51 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28241 Wed 11 Apr 2018 10:43:55 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:32778 Wed 07 Feb 2024 16:54:46 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47747 Tue 21 Mar 2023 19:00:49 AEDT ]]> https://ogma.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://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25887 Thu 21 Jul 2022 15:37:04 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:24426 Thu 04 Nov 2021 10:39:39 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:7415 Sat 24 Mar 2018 08:40:26 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:11170 Sat 24 Mar 2018 08:10:42 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:16697 Sat 24 Mar 2018 08:06:52 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21393 = 30 kg/m²) had slightly poorer OS (hazard ratio [HR] = 1.19; 95% CI, 0.99 to 1.44) than patients with normal BMI (< 25 kg/m²), whereas no trend in OS was observed in overweight (BMI 25 to < 30 kg/m²) versus normal-weight patients (HR = 1.02; 95% CI, 0.86 to 1.20). Treatment-by-BMI interactions were not statistically significant. The HRs for OS comparing obese versus normal BMI were HR = 1.22 (95% CI, 0.93 to 1.60) and HR = 1.18 (95% CI, 0.91 to 1.52) in the letrozole and tamoxifen groups, respectively. Conclusion: There was no evidence that the benefit of letrozole over tamoxifen differed according to patients' BMI.]]> Sat 24 Mar 2018 08:05:04 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21497 Sat 24 Mar 2018 08:03:39 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17404 Sat 24 Mar 2018 08:01:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:5363 Sat 24 Mar 2018 07:43:57 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29018 P = .14) and in triple-negative (TN) disease (n = 814; HR, 0.80; 95% CI, 0.60 to 1.06). Patients with TN, node-positive disease had a nonstatistically significant reduced HR (n = 340; HR, 0.72; 95% CI, 0.49 to 1.05). Seventy-one (13%) of 542 patients assigned to CM maintenance did not start CM. Of 473 patients who received at least one CM maintenance dose (including two patients assigned to no CM), 64 (14%) experienced a grade 3 or 4 treatment-related adverse event; elevated serum transaminases was the most frequently reported (7%), followed by leukopenia (2%). Conclusion: CM maintenance did not produce a significant reduction in DFS events in hormone receptor-negative early breast cancer. The trend toward benefit observed in the TN, node-positive subgroup supports additional exploration of this strategy in the TN, higher-risk population.]]> Sat 24 Mar 2018 07:31:09 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23220 Sat 24 Mar 2018 07:10:38 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41881 Mon 15 Aug 2022 14:09:04 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44148 Mon 10 Oct 2022 09:17:25 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30333 Fri 01 Apr 2022 09:24:55 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29891 Fri 01 Apr 2022 09:22:24 AEDT ]]>