Utilization of Systemic Therapy in Patients With Cancer Near the End of Life in the Pre- Versus Postimmune Checkpoint Inhibitor Eras

Abstract

PURPOSE: Systemic therapy use in the last 30 days of life (DOL) for patients with advanced cancer is a low-value medical practice. We hypothesized that systemic therapy use in the last 30 DOL increased after approval of antiprogrammed cell death protein 1 immune checkpoint inhibitors (ICIs) and has contributed to increased health care utilization and spending. METHODS: We investigated the change in prevalence of any systemic therapy use in the last 30 DOL among patients with advanced solid tumors in the 4 years before and after antiprogrammed cell death protein 1 ICI approval in 2014. We used cases from the Western Washington Cancer Surveillance System linked to commercial and Medicare insurance. We calculated the difference in prevalence between the pre- and post-ICI periods. We also calculated the annual prevalence of any systemic therapy and ICI use in the last 30 DOL and measured health care utilization (emergency department visits and hospitalizations) and costs during the last 30 DOL. RESULTS: Eight thousand eight hundred seventy-one patients (median age 73 years) were included; 34% and 66% in the pre-and post-ICI period, respectively. Systemic therapy use in the last 30 DOL was lower in the post-ICI versus pre-ICI period (12.4% v 14.4%; difference −2.0% [95% CI, −3.5 to −0.5]). The annual prevalence of systemic therapy use in the last 30 DOL also declined, although ICI use rose. Patients treated with ICIs in last 30 DOL had more emergency department visits, hospitalizations, and higher costs. CONCLUSION: Systemic therapy use in the last 30 DOL was lower in the period after ICI approval. However, ICI use rose over time and had higher utilization and costs in the last 30 DOL. Systemic therapy use in the last 30 DOL warrants monitoring, especially as more ICI indications are approved.

Administration of Immune Checkpoint Inhibitors Near the End of Life

“…Our findings reinforce the data generated by others describing increasing ICI utilization or high rates of ICI use near the EOL. [7][8][9][10][11][12] A recent study from 2019 found that ICI use at the EOL had increased significantly in those with poor ECOG PS but did not increase significantly in those with good ECOG PS. 12 In our study, over 50% of patients had a ECOG PS of $ 2, including 17% of patients with a ECOG PS of 3.…”

“…[2][3][4][5][6] Despite the widespread adoption of ICIs into clinical practice, only a few studies have investigated their use at the end of life (EOL). [7][8][9][10][11][12][13] While ICIs may be believed to be better tolerated in comparison with cytotoxic chemotherapy, the decision to use ICIs in those with advanced cancer often carries a degree of uncertainty for both patients and physicians. Predicting treatment response to ICIs is challenging because of variations by tumor type and limited reliability of biomarkers.…”

“…9 In a study of all patients with solid tumors in 2018, ICIs made up 25% of all systemic therapy given in the last 30 days of life. 7 Identification of variables associated with ICI use at EOL has been limited to this point. In a study of all patients with cancer who had received ICIs between 2015 and 2018, 27% had received an ICI in the last 30 days of life.…”

“…10 Additionally, ICI use in the last 30 days of life in patients with solid tumors was found to be more costly than other forms of systemic therapy. 7 Given these trends, we sought to better define this group of patients and variables associated with such practice at our large academic institution. To our knowledge, this is the first study that comprehensively characterizes a substantial number of patients with associated relevant variables such as ECOG PS, rates of hospitalization and intensive care unit (ICU) stays, and other clinical factors in those patients receiving ICIs in the last 30 days of life.…”

Immunotherapy in Patients With Poor Performance Status: The Jury Is Still Out on This Special Population

“…17 Multiple studies have shown that ICI use near the end of life can also lead to negative outcomes, including delays in hospice referrals, more emergency department visits, hospital admissions, and more patients dying in the hospital. 13,[18][19][20][21] The promise of ICIs also leads patients with debility from cancer or other comorbidities to pursue rehabilitation near the end of life and hold on to hope for further therapy, although few successfully reach this goal. 22 These findings suggest that in pursuing ICI therapy with uncertain or low likelihood of benefit, patients and clinicians may defer important discussions about prognosis and patient preferences for end-of-life care and results in higher health care utilization.…”