Trends in Checkpoint Inhibitor Therapy for Advanced Urothelial Cell Carcinoma at the End of Life: Insights from Real-World Practice

Abstract

Because immune checkpoint inhibitor therapies (CPI) lack the toxicities of chemotherapy, oncologists may prescribe CPI to patients at the end of life. This article describes real‐world patterns of CPI initiation near the end of life among individuals with metastatic urothelial cell carcinoma.

Impact of performance status on treatment outcomes: A real‐world study of advanced urothelial cancer treated with immune checkpoint inhibitors

“…However, since the initial approval of atezolizumab in 2016, ICIs have changed the treatment landscape for aUC. Because ICIs are generally better tolerated than chemotherapy, much higher use has been reported near the end of life (EOL) and among those with a poor PS despite limited data from clinical trials regarding benefit in this population. Recent accelerated FDA approval of erdafitinib for tumors harboring FGFR2/3 alterations and promising results in phase 2 trials with other targeted therapies and antibody drug conjugates, such as enfortumab‐vedotin, sacituzumab govitecan (IMMU‐132), and anti‐HER2 compounds, can further increase nonchemotherapy treatment options for aUC .…”

“…A study of ICI utilization practices with the Flatiron Health data set showed that 23% of patients with urothelial cancer were treated with ICIs in the final 30 DOL and that at least 38% of those patients had an ECOG PS ≥ 2 at the start of ICI treatment. 13 In addition, a single-institution, retrospective cohort study by Glisch et al 33 investigated ICI use (across tumor types) near the EOL and found that 27% of the patients in their cohort of 157 patients were treated with ICIs in the last 30 DOL; ICI use in the last 30 DOL was associated with lower hospice enrollment and a higher chance of dying in the hospital. In our study, only 10% had ICI initiation in the last 30 DOL; however, ICI initiation near the EOL was associated with higher odds of dying in the hospital.…”

“…The perceived favorable toxicity profile of ICIs has led to the selection of these agents for patients otherwise unfit for systemic chemotherapy. Real‐world utilization patterns have shown an increase in ICI use for aUC within 60 days of death from 1% in the final quarter of 2015 to 23% in the final quarter of 2017, with at least 38% of those treated having a recorded ECOG PS ≥ 2 at the start of treatment …”

“…Real-world utilization patterns have shown an increase in ICI use for aUC within 60 days of death from 1% in the final quarter of 2015 to 23% in the final quarter of 2017, with at least 38% of those treated having a recorded ECOG PS ≥ 2 at the start of treatment. 13 However, there is a paucity of data supporting the use of ICIs in patients with a poor PS, who were not very well represented in the clinical trials that led to their approval, with no trial enrolling patients with an ECOG PS ≥ 3 and only 3 trials including patients with an ECOG PS of 2. 2,7,8 In addition, an ECOG PS ≥ 3 has been associated with an imbalance in circulating CD8+ and CD4+ T lymphocytes in patients with gastric cancer, and this raises the concern that ICIs may be less effective in these patients.…”

Comparison of Population Characteristics in Real-World Clinical Oncology Databases in the US: Flatiron Health, SEER, and NPCR

“…SEER and NPCR have been well established as research resources since their inception in 1973 and 1992, respectively. As the most recent of the three sources, data derived from Flatiron Health have become a research resource in the last five years (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18); therefore, it has become increasingly critical to understand their features. SEER and NPCR collect specific incident disease data points in a systematic and ordered fashion, fulfilling a public health reporting mandate justified by the public health burden of cancer as a disease.…”