The lancet oncology
-
The lancet oncology · Oct 2024
ReviewInterchangeability of immune checkpoint inhibitors: an urgent need for action.
Prevailing uncertainties regarding the therapeutic interchangeability of PD-1 and PD-L1 inhibitors affect both clinical decision making and health-care budgeting. This Personal View presents a comprehensive assessment of the fragmented regulatory landscape of PD-1 and PD-L1 inhibitors, highlighting the complex dynamics of market competition, pricing, and the effect on health-care budgets. ⋯ To address these challenges, research that will inform us of the extent of interchangeability of PD-1 and PD-L1 inhibitors is needed. We recommend head-to-head randomised controlled trials, standardised study designs for indirect comparisons, trials with monotherapy groups, post-approval trials funded from private or public sources, and adoption of a near-equivalence framework in both conducting and evaluating trials.
-
The lancet oncology · Oct 2024
ReviewDevelopment of a conceptual framework for an electronic patient-reported outcome (ePRO) system measuring symptoms and impacts of CAR T-cell therapies in patients with haematological malignancies.
Chimeric antigen receptor (CAR) T-cell therapy is associated with potentially severe toxicities that create a substantial burden for patients. Patient-reported outcomes (PROs) offer valuable insights into symptoms, functioning, and other complex constructs of interest. In this Review, we aimed to identify symptom and impact concepts important to patients receiving CAR T-cell therapy, construct a conceptual framework for an electronic patient-reported outcome (ePRO) system, and identify timepoints to capture PRO data for CAR T-cell therapies. ⋯ Six health-care professionals and 11 patients and caregiver partners verified construct relevance to clinical management and lived experience, respectively. 109 constructs were sorted according to the four domains of conceptual framework: symptom burden, impact of disease and treatment, tolerability, and health-related quality of life. The identification of concepts beyond symptom burden underscores the importance of PRO measurement for long-term monitoring, to align outcomes with patient concerns. The framework will facilitate PRO measure selection for systematic gathering of PROs from individuals with haematological malignancies receiving CAR T-cell therapies.
-
The lancet oncology · Oct 2024
ReviewBest practices and novel approaches for the preclinical development of drug-radiotherapy combinations for cancer treatment.
Drug-radiation combination therapy is a practical approach to improving clinical outcomes for many tumours. Unfortunately, most clinical combination studies combine drugs with radiotherapy empirically and do not exploit mechanistic synergy in cell death and the interconnectivity of molecular pathways of tumours or rationale for selecting the dose, fractionation, and schedule, which can result in suboptimal efficacy and exacerbation of toxic effects. However, opportunities exist to generate compelling preclinical evidence for combination therapies from fit-for-purpose translational studies for simulating the intended clinical study use scenarios with standardised preclinical assays and algorithms to evaluate complex molecular interactions and analysis of synergy before clinical research. Here, we analyse and discuss the core issues in the translation of preclinical data to enhance the relevance of preclinical assays, in vitro clonogenic survival along with apoptosis, in vivo tumour regression and growth delay assays, and toxicology of organs at risk without creating barriers to innovation and provide a synopsis of emerging areas in preclinical radiobiology.
-
The lancet oncology · Oct 2024
ReviewChallenges and opportunities for early phase clinical trials of novel drug-radiotherapy combinations: recommendations from NRG Oncology, the American Society for Radiation Oncology (ASTRO), the American College of Radiology (ACR), the Sarah Cannon Research Institute, and the American College of Radiation Oncology (ACRO).
NRG Oncology's Developmental Therapeutics and Radiation Therapy Subcommittee assembled an interdisciplinary group of investigators to address barriers to successful early phase clinical trials of novel combination therapies involving radiation. This Policy Review elucidates some of the many challenges associated with study design for early phase trials combining radiotherapy with novel systemic agents, which are distinct from drug-drug combination development and are often overlooked. We also advocate for potential solutions that could mitigate or eliminate some of these barriers, providing examples of specific clinical trial designs that could help facilitate efficient and effective evaluation of novel drug-radiotherapy combinations.
-
The lancet oncology · Oct 2024
Meta AnalysisEfficacy and safety of immune checkpoint inhibitors for individuals with advanced EGFR-mutated non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitors: a systematic review, meta-analysis, and network meta-analysis.
The clinical benefits of immune checkpoint inhibitor (ICI)-based treatments in treating individuals with advanced EGFR-mutated non-small-cell lung cancer (NSCLC) who have progressed on EGFR tyrosine-kinase inhibitors (TKIs) remain controversial. We aimed to review the literature to comprehensively investigate the individual and comparative clinical outcomes of various ICI-based treatment strategies in this population. ⋯ None.