In other news: Focus on clinical trial endpoints
medwireNews: This month’s round-up covers three studies evaluating clinical trial endpoints, two focusing on endpoints for programmed cell death protein 1 (PD-1) inhibitor trials and one assessing the surrogacy of progression-free survival (PFS) in the first-line diffuse large B-cell lymphoma (DLBCL) setting. Read on for more details.
PFS does not adequately capture the benefits of anti-PD-1 agents and “overall survival [OS] should remain the gold standard end point” for trials of these agents, say Bishal Gyawali (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and co-authors, who conducted a meta-analysis of 12 trials including a total of 5417 participants with solid cancers.
As reported in JAMA Network Open, there was no significant correlation between OS and PFS in terms of either median values or gains in the median relative to nonimmunotherapy controls. And although the hazard ratios for the endpoints did correlate significantly, PD-1 inhibitors appeared to have a greater effect on OS than PFS, a finding the authors describe as “unprecedented in oncology therapeutics.”
Using specimens from 20 non-small-cell lung cancer (NSCLC) patients enrolled in a trial of neoadjuvant nivolumab, researcher Janis Taube (Johns Hopkins University, Baltimore, Maryland, USA) and colleagues have identified specific histologic features of immune-mediated response, such as the presence of dense tumor infiltrating lymphocytes with macrophages and tertiary lymphoid structures.
They used these features to develop a novel scoring system called the immune-related pathologic response criteria (irPRC), which “promoted higher reproducibility amongst the pathologists” participating in the study.
The “irPRC may be used to standardize pathologic assessment of immunotherapeutic efficacy,” but “[l]ong-term follow-up is needed to determine irPRC reliability as a surrogate for recurrence-free and overall survival,” the team writes in the Annals of Oncology.
A pooled analysis of individual data from 7507 participants of 13 trials of chemoimmunotherapy agents for newly diagnosed DLBCL indicates that PFS can serve as a surrogate endpoint for OS in future trials.
Qian Shi, from the Mayo Clinic in Rochester, Minnesota, USA, and co-researchers report that the correlation between PFS and OS was “strong” at both the trial and patient level, indicating that “treatment effect on PFS is a strong predictor of treatment effect on OS.”
They conclude in the Journal of Clinical Oncology: “Use of this end point may expedite therapeutic development with the intent of bringing novel therapies to this patient population years before OS results are mature.”
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