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BackgroundThe rationale for the evaluation of trametinib in advanced biliary cancer (BC) is based on the presence of mitogen-activated protein kinase alterations and on earlier promising results with MEK inhibitors in BC.MethodsPatients with histologically proven BC who progressed on gemcitabine/platinum were randomised to trametinib daily (arm 1) versus fluoropyrimidine therapy (infusional 5-fluorouracil or oral capecitabine, arm 2). The primary end-point was overall survival (OS). Secondary end-points included progression free survival (PFS) and response rate. A planned interim futility analysis of objective response was performed on the first 14 patients registered to the trametinib arm.ResultsThe study was stopped early based on the lack of measurable response in the trametinib arm. A total of 44 eligible patients were randomised (24 patients in arm 1 and 20 patients in arm 2). Median age was 62 years and the primary sites of tumour were cholangiocarcinoma (68%) and gallbladder (32%). The overall response rate was 8% (95% CI 0%-19%) in arm 1 versus 10% (95% CI 0%-23%) in arm 2 (p > .99) Median OS was 4.3 months for arm 1 and 6.6 months for arm 2. The median PFS was 1.4 months for arm 1 and 3.3 months for arm 2.ConclusionsThis is the first prospective randomised study of a targeted agent versus chemotherapy for the second-line treatment of BC. In this unselected population, the interim analysis result of unlikely benefit with trametinib resulted in early closure.

Introduction: Healthcare providers (HCPs) may face numerous dilemmas in optimally screening, diagnosing, and treating patients with, and/or at risk for, hepatocellular carcinoma (HCC). This study aimed to achieve a greater understanding of the challenges in HCC care which in turn could delineate HCP educational opportunities within this oncologic sub‐specialty. Methods: A mixed‐methods approach was used to identify practice gaps and clinical barriers experienced by US‐based medical oncologists, hepatologists, oncology physician assistants, oncology nurse practitioners, and interventional radiologists involved in HCC care. The qualitative (semi‐structured interview) and quantitative (survey) data collection approaches were deployed sequentially with findings subsequently triangulated. Results: A total of 214 HCPs participated in this study. Analysis revealed challenges related to screening and diagnosing HCC, specifically in applying appropriate screening guidelines, and the optimal use and decisions related to diagnostic imaging and biopsy. Issues related to treatment selection included the application of existing HCC guidelines in treatment decision‐making, weighing risk/benefit ratios of various antineoplastics regimens (i.e., tyrosine kinase inhibitors‐TKIs, immunotherapy agents, chemotherapy), sequencing therapies, potential toxicity management, and optimally educating patients about their HCC. Conclusion: These findings highlight the educational needs of those involved in HCC care and provide a starting point for clinicians to both reflect on their practice and identify opportunities to enhance communication within the HCC team and between provider and patient. There is an opportunity to optimize continuing professional development interventions that address the identified gaps in clinical practice specifically related to teamwork and interdisciplinary communication. [ABSTRACT FROM AUTHOR]

Aim: To assess concordance between HER2 status measured by traditional methods and ERBB2 amplification measured by next-generation sequencing and its association with first-line trastuzumab clinical benefit in patients with advanced esophagogastric cancer. Methods: Retrospective analysis of HER2/ERBB2 concordance using a deidentified USA-based clinicogenomic database. Clinical outcomes were assessed for patients with HER2+ advanced esophagogastric cancer who received first-line trastuzumab. Results: Overall HER2/ERBB2 concordance was 87.5%. Among patients who received first-line trastuzumab, concordant HER2/ERBB2 was associated with longer time to treatment discontinuation (adjusted hazard ratio [aHR]: 0.63; 95% CI: 0.43-0.90) and overall survival (aHR: 0.51; 95% CI: 0.33-0.79). ERBB2 copy number ≥25 (median) was associated with longer time to treatment discontinuation (aHR: 0.56; 95% CI: 0.35-0.88) and overall survival (aHR: 0.52; 95% CI: 0.30-0.91). Conclusion: HER2/ERBB2 concordance and higher ERBB2 copy number predicted clinical benefit from trastuzumab. [ABSTRACT FROM AUTHOR]

Aim: To assess concordance between HER2 status measured by traditional methods and ERBB2 amplification measured by next-generation sequencing and its association with first-line trastuzumab clinical benefit in patients with advanced esophagogastric cancer. Methods: Retrospective analysis of HER2/ ERBB2 concordance using a deidentified USA-based clinicogenomic database. Clinical outcomes were assessed for patients with HER2 + advanced esophagogastric cancer who received first-line trastuzumab. Results: Overall HER2/ ERBB2 concordance was 87.5%. Among patients who received first-line trastuzumab, concordant HER2/ ERBB2 was associated with longer time to treatment discontinuation (adjusted hazard ratio [aHR]: 0.63; 95% CI: 0.43-0.90) and overall survival (aHR: 0.51; 95% CI: 0.33-0.79). ERBB2 copy number ≥25 (median) was associated with longer time to treatment discontinuation (aHR: 0.56; 95% CI: 0.35-0.88) and overall survival (aHR: 0.52; 95% CI: 0.30-0.91). Conclusion: HER2/ ERBB2 concordance and higher ERBB2 copy number predicted clinical benefit from trastuzumab.

Background: To investigate mutational load and histologic biomarkers as prognostic factors in patients with chemorefractory colorectal liver metastases (CRLM) treated with Y-90 radioembolization therapy., Materials and Methods: Single institution retrospective study of patients with CRLM who received Y-90 radioembolization after undergoing molecular testing was performed. Patient demographics, systemic therapy regimens, tumor characteristics and overall survival were analyzed between patients with differing histopathologic and genomic status. PIK3CA, KRAS, NRAS, AKT1, MEK1, MLH1, MSH2, MSH6 and PMS2 were analyzed. Kaplan-Meier survival estimation and multivariate Cox regression were analyzed., Results: 23 patients underwent genomic analysis prior to Y-90. Eleven (47.8%) had mutations identified (MUT), and 12 were sequenced as wild type (WT) (52.2%). Median OS of 23 patients after Y-90 was 9.6 months (95% CI 6.67-16.23). Median OS from first Y-90 was significantly greater in WT patients (16.2 mo vs 6.5 mo; p =.0054). The survival difference between poorly differentiated tumors compared to all other histologic grades was significant (poor vs. well p=0.025, HR=26.8; poor vs. moderate p=.014, HR=23.07; poor vs. moderate/poor p=0.014, HR=23.68). When separated into 3 different groups (WT vs. MUT/moderate differentiation vs. MUT/poor differentiation) there was a difference in median OS observed (16.2 vs. 8.0 vs. 3.8 mos; p<.0001). Imaging response via RECIST criteria was significantly different between MUT and WT groups (p=0.02)., Conclusions: Mutational status and histopathologic grade may predict survival after Y-90 radioembolization therapy for CRLM., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest. All authors have no financial any other relationship to disclose with any commercial organization that may have a direct or indirect interest in this manuscript.

The medical oncologist's perspective on hepatocellular carcinoma (HCC) is unique compared with their view on other solid tumors. A patient's underlying liver function should be factored into the selection of treatment options; therefore, a staging system that takes into account other clinical parameters other than only tumor characteristics is important. Sorafenib is currently the only FDA-approved chemotherapy drug for patients with HCC based on the data from the SHARP trial. It is important for oncologists to anticipate and treat the side effects of sorafenib treatment in order to help the patients continue the treatment. In addition, it is important to design clinical trials for HCC that have meaningful endpoints to improve our care for patients with HCC.