The lancet oncology
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The lancet oncology · Sep 2020
Multicenter StudyDabrafenib plus trametinib in patients with BRAFV600E-mutated biliary tract cancer (ROAR): a phase 2, open-label, single-arm, multicentre basket trial.
Effective treatments for patients with cholangiocarcinoma after progression on gemcitabine-based chemotherapy are urgently needed. Mutations in the BRAF gene have been found in 5% of biliary tract tumours. The combination of dabrafenib and trametinib has shown activity in several BRAFV600E-mutated cancers. We aimed to assess the activity and safety of dabrafenib and trametinib combination therapy in patients with BRAFV600E-mutated biliary tract cancer. ⋯ GlaxoSmithKline and Novartis.
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The lancet oncology · Sep 2020
ReviewTurning up the heat on non-immunoreactive tumours: opportunities for clinical development.
Notable advances have been achieved in the treatment of cancer since the advent of immunotherapy, and immune checkpoint inhibitors have shown clinical benefit across a wide variety of tumour types. Nevertheless, most patients still progress on these treatments, highlighting the importance of unravelling the underlying mechanisms of primary resistance to immunotherapy. ⋯ In this Review, we discuss preclinical data that serves as the basis for ongoing immunotherapy clinical trials for the treatment of non-immunoreactive tumours, as well as reviewing clinical and translational data where available. We explain how improving our understanding of the underlying mechanisms of primary resistance to immunotherapy will help elucidate an increasingly granular view of the tumour microenvironment cellular composition, functional status, and cellular localisation, with the goal of further therapy refinement.
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The lancet oncology · Sep 2020
Randomized Controlled TrialDebio 1143 and high-dose cisplatin chemoradiotherapy in high-risk locoregionally advanced squamous cell carcinoma of the head and neck: a double-blind, multicentre, randomised, phase 2 study.
Debio 1143 is an orally available antagonist of inhibitor of apoptosis proteins with the potential to enhance the antitumour activity of cisplatin and radiotherapy. The radiosensitising effect of Debio 1143 is mediated through caspase activation and TNF, IFNγ, CD8 T cell-dependent pathways. We aimed to investigate the efficacy and safety of Debio 1143 in combination with standard chemoradiotherapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck. ⋯ Debiopharm.
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The lancet oncology · Sep 2020
Randomized Controlled TrialSecond-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP-PRODIGE 15): a randomised, phase 3 study.
Diagnosis and treatment of colorectal peritoneal metastases at an early stage, before the onset of signs, could improve patient survival. We aimed to compare the survival benefit of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC), with surveillance, in patients at high risk of developing colorectal peritoneal metastases. ⋯ French National Cancer Institute.
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The lancet oncology · Sep 2020
Randomized Controlled TrialEffect of mammographic screening from age 40 years on breast cancer mortality (UK Age trial): final results of a randomised, controlled trial.
The appropriate age range for breast cancer screening remains a matter of debate. We aimed to estimate the effect of mammographic screening at ages 40-48 years on breast cancer mortality. ⋯ National Institute for Health Research Health Technology Assessment programme.