5515 Background: Cyclin E1 gene amplification and protein over-expression is a marker of platinum resistance in high grade serous ovarian, fallopian tube or primary peritoneal cancer (HGSC), and may predict response to WEE1 inhibition. Adavosertib, a WEE1 inhibitor, has demonstrated activity in unselected women with recurrent ovarian and serous endometrial cancer. We aimed to evaluate the efficacy of adavosertib in women with recurrent platinum resistant HGSC with cyclin E1 over-expression, with and without gene amplification. Methods: IGNITE is a multicentre, phase 2 trial with 2 cohorts of women with recurrent platinum resistant HGSC. Tumors were assessed for cyclin E1 protein expression by IHC and CCNE1 copy number by FISH. Patients were assigned to Cohort 1 if tumors were cyclin E1 over-expressed (H-score>50) and amplified (≥8 copies), and Cohort 2 if tumors were overexpressed and nonamplified. Patients with evaluable disease by RECIST v1.1 or GCIG CA-125 criteria were included. Adavosertib 300mg PO was given daily on days 1-5 and 8-12 of a 21-day cycle. The primary endpoint was investigator assessed clinical benefit (CB) defined as absence of progression for ≥ 18 weeks. Here we present the 18-week response data for the first 32 patients treated from Cohort 2, with a data cut-off of August 2021. Results: Between Jan-2020 and May-2021, 32 patients were accrued to Cohort 2. Median age was 62 years (range 42-77) and 84% had received ≥2 prior lines of chemotherapy. Median cyclin E1 IHC H-score was 120 and 28 patients (88%) had measurable disease by RECIST. Median number of cycles commenced was 8 (range 1-19). Overall response rate (ORR) was 53% and CB rate was 61% for all evaluable patients. Seventeen patients (53%) required a dose reduction, most commonly for neutropenia or fatigue. Seventeen patients experienced ≥Grade 3 treatment related adverse event, and 4 patients (15%) discontinued due to toxicity. Conclusions: The efficacy results in a biomarker-selected cohort of patients are promising with a higher response rate than reported in previous studies of adavosertib in unselected women with recurrent HGSC. Duration of response and progression free survival data will be presented as data matures. Clinical trial information: ACTRN12619001185156P. [Table: see text]
Background Patients with early-stage (cT2-3N0) rectal cancer undergoing standard care upfront resection remain a poorly studied patient group with limited literature reporting the impact of adverse pathological features and surgical complications. This study aimed to characterise outcomes in patients with early-stage rectal cancer undergoing upfront Total Mesorectal Excision (TME). Methods This is a retrospective, multi-centre, statewide study of patients with cT2-3N0 rectal adenocarcinoma without high-risk clinical staging characteristics (extramural vascular invasion [EMVI] or threatened/involved mesorectal fascia on MRI) undergoing upfront TME from 2013 to 2025 in South Australia. The main outcome measure was a composite of adverse pathological features, defined as: R1 resection, pT4 disease, nodal upstaging, or EMVI. Operative and oncological outcomes were collected and used to determine rates of Textbook Outcome (TO). The impact of adverse pathological features on 3-year disease-free survival (DFS) and overall survival (OS) was analysed. Results Among 120 patients with cT2-3N0 rectal cancer undergoing upfront surgery, at least one adverse pathological feature was present in 35.8% of patients, increasing to 50% in patients with low rectal cancer. 3-year DFS rates were 84% (95% CI 75-93) without adverse pathological features, and 72% (95% CI 57-87) in patients with at least one adverse pathological feature (p = 0.167). 3-year OS rates were 94% (95% CI 88-100) without adverse pathological features, and 92% (95% CI 83-100) in patients with at least one adverse pathological feature (p = 0.617). TO was achieved in 57.5%, and 39.2% of patients experienced an ideal short term outcome (no adverse pathological features and TO achieved). Conclusion There is a considerable margin, nodal and EMVI upstaging rate in patients with early-stage rectal cancer undergoing standard care upfront TME, particularly those with low tumours. This highlights the limitations of current clinical staging in rectal cancer, leading to early-staged patients potentially being undertreated.
Autoantibodies against NOR-90 are rare and have been associated with systemic sclerosis (SSc). This study seeks to identify the characteristics of SSc participants with anti-NOR-90 autoantibodies. An international (Canada, Australia, USA, Mexico) cohort of 2143 SSc participants was included. Sera were tested using a line immunoassay (Euroimmun, Lübeck, Germany). Clinical associations with anti-NOR-90 autoantibodies were investigated. Single-specificity anti-NOR-90-positive was defined as anti-NOR-90-positivity without other SSc-related autoantibodies, except for anti-Ro52/TRIM21. 115 (5
