fore, combined anti-MEK and anti-CDK4 and anti-CDK6 therapy may be a potential therapeutic option in RAF fusion-driven tumors. Methods A complete description of the methods is provided in the Supplemental Material. Study approval. All experiments were performed under protocols reviewed and approved by iPREDICT (approval no. HREC/13/ MH/326) and SUPER (Solving Unknown Primary cancER) (approval no. 11/117) studies and the Peter MacCallum Cancer Centre (Melbourne, Australia). 1 9 4 5 jci.org Volume 129 Number 5 May 2019 assistance with GRIDSS (Genome Rearrangement IDentification Software Suite) analysis; Jason Li for setting up the analysis pipeline for the nCounter data set; Jenna Stewart and David Yoannidis for technical assistance; Kelly Waldek for advice on IHC; Chung-Yan Ma for discussions on immunomarkers; and Michael McKay and Glen Gurra for critical discussions of the manuscript.

BackgroundMetastatic colorectal cancer (mCRC) patients with a right sided primary (RC) have an inferior survival to mCRC arising from a left sided primary (LC). Previous analyses have suggested multiple factors contribute. MethodsThe Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) Registry prospectively captured data on consecutive mCRC patients. RC were defined as tumors proximal to the splenic flexure; LC were those at and distal to the splenic flexure and included rectal cancers.Patient, tumor, treatment and survival data were analysed stratified by side. ResultsOf 2306 patients enrolled from July 2009 -March 2018, 747 (32%) had a RC. Patients with RC were older, more likely to be female and have a Charlson score ≥ 3. RC were more frequently BRAF mutated, deficient in mismatch repair, associated with peritoneal metastases and less likely to receive chemotherapy. Progression-free survival on first line systemic therapy was inferior for RC patients (8.1 vs 10.8 months, hazard ratio [HR] 1.38, p<0.001). Median overall survival (OS) for all RC patients was inferior (19.6 vs 27.5 months, HR 1.44, p<0.001), and inferior within the treated (21 vs 29.5 months, HR 1.52, p<0.001) and untreated subgroups (5.9 vs 10.3 months, HR 1.38, p=0.009).Primary side remained a significant factor for OS in multivariate analysis. ConclusionOur data from a real-world population confirms the poorer prognosis associated with RC. Primary tumor location remains significantly associated with overall survival even when adjusting for multiple factors, indicating the existence of further side-based differences that are as yet undefined.

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Background The impact of regulatory approvals of new therapies for castration‐resistant prostate cancer (CRPC) in Australia is unclear. Aims To determine if changes in novel therapy access in Australia affected how clinicians initially managed men with newly diagnosed CRPC. Methods Data from patients diagnosed with CRPC from 2013 to 2016 across three Australian hospitals were retrospectively collected. Baseline clinicopathological factors and initial management decision at the time of CRPC development (early treatment (ET) vs deferred treatment (DT)) were recorded. Categorical variables between cohorts were compared by Chi‐squared analysis. Cox regression analysis was performed to assess the impact of CRPC diagnosis year on time to commencing life‐prolonging systemic treatment (TTT). Results Our study identified 137 CRPC patients, with 126 (92%) patients receiving life‐prolonging systemic treatment. The median age was 73 years. The initial management decision was DT in 71 (52%) patients and ET in 66 (48%) patients. There was a significant shift from DT to ET during the study period (2013–2014: DT 61% vs ET 33%; 2015–2016: DT 39% vs ET 67%; P = 0.004), with a rise in novel androgen receptor signalling inhibitor use and simultaneous reduction in first‐generation antiandrogen use at CRPC development. Each successive CRPC diagnosis year was associated with shorter TTT on univariate analysis (HR: 1.5, 95% CI: 1.3–1.7, P < 0.001). Conclusion Over time, clinicians are favouring earlier introduction of life‐prolonging systemic treatment at the development of CRPC. This trend is largely driven by substantial uptake of novel androgen receptor signalling inhibitors as the preferred initial treatment for CRPC patients.