The Association Between Baseline Hepatic or Renal Function and Clinical Outcomes for Patients With Non‐Small Cell Lung Cancer Treated With a PD‐1/PD‐L1 Blocking Antibody Using Real‐World and Trial Data

Abstract

Clinical trials have demonstrated the benefit of PD‐1/PD‐L1 blocking antibodies for the treatment of patients with advanced non‐small cell lung cancer (NSCLC) in defined patient populations that often exclude patients with moderate or severe hepatic or renal impairment. We assessed the association between overall survival (OS) and baseline organ function in patients with advanced NSCLC treated with PD‐1/PD‐L1 blocking antibodies in real‐world data (RWD; patient‐level data from electronic health records) and pooled clinical trial data submitted to the US Food and Drug Administration (FDA). The Kaplan–Meier estimator was used to estimate OS in different subgroups based on organ function. Unadjusted and adjusted Cox proportional hazards models were used to estimate the association between OS and organ function. In this hypothesis‐generating study, baseline renal impairment did not appear to be associated with OS, while patients with baseline liver impairment had shorter OS. RWD provided information on a broader range of renal and hepatic function than was evaluated in clinical trials and hold promise to complement trial data in better understanding populations not represented in clinical trials.

Signal detection in real‐world data and confirmation in clinical trials: Diabetes as a case study for a conversation worth having

“…2 At the same time, a revolution in real-world data (RWD) has been emerging from the rapid digitization of electronic health records, with numerous industry and academic analyses of patient data, allowing for improved understanding of patient outcomes outside of clinical trials. [3][4][5] In the accompanying article by Leshem et al, 6 the investigators used two separate databases to evaluate the effect of diabetes on outcomes for patients with non-small cell lung cancer being treated with immune checkpoint inhibitors, either alone or in combination with chemotherapy. The investigators found a difference in survival outcomes when comparing diabetic patients to nondiabetic patients.…”

Advancing the utilization of real‐world data and real‐world evidence in clinical pharmacology and translational research—Proceedings from the ASCPT 2023 preconference workshop

“…In one collaborative research project, both RWD and pooled clinical trial data were used to assess the association between OS and baseline organ function in patients with advanced NSCLC treated with PD‐1/PD‐L1 blocking antibodies. 26 Both RWD and clinical trial data suggested that baseline renal impairment did not appear to be associated with OS, while patients with baseline liver impairment had shorter OS. In addition, RWD included patients over a broader range of renal and hepatic function than was enrolled in clinical trials.…”

“…OCP has also been working on many collaborative research projects to identify where RWE can be most helpful and to develop best practices to advance RWE for clinical pharmacology. In one collaborative research project, both RWD and pooled clinical trial data were used to assess the association between OS and baseline organ function in patients with advanced NSCLC treated with PD‐1/PD‐L1 blocking antibodies 26 . Both RWD and clinical trial data suggested that baseline renal impairment did not appear to be associated with OS, while patients with baseline liver impairment had shorter OS.…”

Advancing Truth in Oncology by Complementing Clinical Trials With Evidence From Clinical Practice

“…Thus, when patients ask the question as to whether or not a given approved therapy is right for them, it should be possible to find data from similar patients with the same conditions to determine the answer. Other efforts have shown the benefits of immunotherapy to specific subpopulations, such as in patients with melanoma or lung cancer with co-occurring kidney or liver dysfunction, or for patients with certain rare comorbid conditions . When there are multiple choices, this kind of information can be particularly important for patients and clinicians when determining the best available therapy.…”