The lancet oncology
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The lancet oncology · Aug 2024
ReviewDose selection of novel anticancer drugs: exposing the gap between selected and required doses.
Historically, dose selection of anticancer drugs has mainly been based on establishing the maximum tolerated dose in phase 1 clinical trials with a traditional 3 plus 3 design. In the era of targeted therapies and immune-modulating agents, this approach does not necessarily lead to selection of the most favourable dose. This strategy can introduce potentially avoidable toxicity or inconvenience for patients. ⋯ In this Review, we evaluate the rationale and validation of dose selection in each phase of drug development for anticancer drugs approved by the European Medicines Agency and US Food and Drug Administration from Jan 1, 2020, to June 30, 2023, and give recommendations for dose optimisation to improve safety and patient convenience. In our evaluation, we classified 20 (65%) of the 31 recently registered anticancer agents as potential candidates for dose optimisation, which could be achieved either by reducing the dose (n=10 [32%]) or adjusting the dosage regimen (n=10 [32%]). Dose selection seemed to be adequately justified for nine (29%) of the drugs, whereas the reviewed data were inconclusive for formulating a recommendation on dose optimisation for two (6%) of the drugs.
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The lancet oncology · Aug 2024
Randomized Controlled Trial Comparative StudySite-specific therapy guided by a 90-gene expression assay versus empirical chemotherapy in patients with cancer of unknown primary (Fudan CUP-001): a randomised controlled trial.
Empirical chemotherapy remains the standard of care in patients with unfavourable cancer of unknown primary (CUP). Gene-expression profiling assays have been developed to identify the tissue of origin in patients with CUP; however, their clinical benefit has not yet been demonstrated. We aimed to evaluate the efficacy and safety of site-specific therapy directed by a 90-gene expression assay compared with empirical chemotherapy in patients with CUP. ⋯ For the Chinese translation of the abstract see Supplementary Materials section.
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The lancet oncology · Aug 2024
Multicenter StudyMulti-organ immune-related adverse events from immune checkpoint inhibitors and their downstream implications: a retrospective multicohort study.
Understanding co-occurrence patterns and prognostic implications of immune-related adverse events is crucial for immunotherapy management. However, previous studies have been limited by sample size and generalisability. In this study, we leveraged a multi-institutional cohort and a population-level database to investigate co-occurrence patterns of and survival outcomes after multi-organ immune-related adverse events among recipients of immune checkpoint inhibitors. ⋯ US National Institutes of Health.
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Radiotherapy exerts immunostimulatory and immunosuppressive effects, both locally, within the irradiated tumour microenvironment, and systemically, outside the radiation field. Inspired by preclinical data that showed synergy between radiotherapy and immune checkpoint inhibitors, multiple clinical trials were initiated with the hypothesis that combined treatment with radiotherapy and immune checkpoint inhibitors could stimulate a robust systemic immune response and improve clinical outcomes. ⋯ We also discuss findings from clinical trials incorporating radiotherapy and immune checkpoint inhibitors and examine the success of these trials in the context of the immunosuppressive effects of radiotherapy. We conclude by highlighting targets for relieving radiotherapy-induced immunosuppression with the goal of enhancing the combined effects of radiotherapy and immune checkpoint inhibitors.
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The lancet oncology · Aug 2024
Multicenter StudyCeliac plexus radiosurgery for pain management in advanced cancer: a multicentre, single-arm, phase 2 trial.
Refractory upper abdominal pain or lower back pain (retroperitoneal pain syndrome) related to celiac plexus involvement characterises pancreatic and other upper gastrointestinal malignancies and is an unmet need. We hypothesised that ablative radiation delivered to the celiac plexus would decrease pain. ⋯ Gateway for Cancer Research and the Israel Cancer Association.