Immune Checkpoint Inhibitor Use Near the End of Life: A Single-Center Retrospective Study

Glisch, Chad; Saeidzadeh, Seyedehtanaz; Snyders, Travis; Gilbertson‐White, Stephanie; Hagiwara, Yuya; Lyckholm, Laurie

doi:10.1089/jpm.2019.0383

Cited by 28 publications

(31 citation statements)

References 6 publications

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“…In addition, the use of ICI near the EOL in the overall cohort was associated with increased health care utilization, namely, increased hospitalization and in‐hospital death, decreased referral to hospice, and shorter hospice length of stay, regardless of PS. These findings are consistent with results from another study of EOL health care utilization among a cohort of patients with a range of cancer types who received ICIs close to death . The mechanism of the relation between ICI use close to death and higher intensity EOL health care utilization warrants further study.…”

Section: Discussionsupporting

confidence: 88%

Performance status and end‐of‐life care among adults with non–small cell lung cancer receiving immune checkpoint inhibitors

Petrillo

El‐Jawahri

Nipp

et al. 2020

Cancer

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BACKGROUND: Adults with impaired performance status (PS) often receive immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) despite limited efficacy data and unknown effects on end-of-life care. METHODS: This was a retrospective, single-site study of 237 patients with advanced NSCLC who initiated ICI treatment from 2015 to 2017. Cox regression was used to compare the overall survival (OS) of patients who had impaired PS (≥2) at the start of ICI treatment with those who had PS 0 or 1 using Cox regression. Logistic regression was conducted to analyze the association between ICI use in the last 30 days of life and the use of end-oflife health care. RESULTS: The patient mean age at ICI initiation was 67 years (range, 37-91 years), and 35.4% of patients had PS ≥2. Most patients (80.8%) received ICI as second-line or later therapy. The median OS was 4.5 months in patients with PS ≥2 and 14.3 months in those with PS 0 or 1 (hazard ratio, 2.5; P < .0001). Among the patients who died (n = 184), 28.8% who had PS ≥2 received ICIs in their last 30 days of life compared with 10.8% of those who had PS 0 or 1 (P = .002). Receipt of ICI in the last 30 days of life was associated with decreased hospice referral (odds ratio, 0.29; P = .008) and increased in-hospital deaths (odds ratio, 6.8; P = .001), independent of PS. CONCLUSIONS: Adults with advanced NSCLC and impaired PS experience significantly shorter survival after ICI treatment and receive ICIs near death more often than those with better PS. Receipt of an ICI near death was associated with lower hospice use and an increased risk of death in the hospital. These results underscore the need for high-quality communication about potential tradeoffs of ICIs, particularly among adults receiving ICIs as second-line or later therapy. Cancer 2020;126:2288-2295.

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Section: Discussionsupporting

confidence: 88%

Performance status and end‐of‐life care among adults with non–small cell lung cancer receiving immune checkpoint inhibitors

Petrillo

El‐Jawahri

Nipp

et al. 2020

Cancer

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“…Although ICIs might be safer than traditional chemotherapy in patients with impaired PS, we must note that more than 10% of patients with PS ≥2 experienced grade III or worse adverse events in our study. Moreover, ICI use near the end of life is associated with financial difficulties and lower hospice enrollment 8,18 . Given the ORR of 2.6% and mortality rate of 78.9% within 3 months in patients with PS ≥2 and the two aforementioned risk factors (NLR ≥3.5 and liver metastasis), the initiation of pembrolizumab for these patients should be carefully considered with detailed discussion.…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab for treating advanced urothelial carcinoma in patients with impaired performance status: Analysis of a Japanese nationwide cohort

et al. 2021

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BackgroundThe benefits of pembrolizumab in patients with advanced urothelial carcinoma (UC) and impaired performance status (PS) remain unknown. This study assessed the safety and efficacy of pembrolizumab in patients with platinum‐refractory UC and Eastern Cooperative Oncology Group PS ≥2 to identify which subgroups may benefit from this drug.MethodsThis retrospective nationwide cohort study collected clinicopathological information for 755 patients from 59 institutions. The overall response rate (ORR) and overall survival (OS) were compared among the patients with PS 0–1, 2, and 3–4. Multivariate analysis was conducted to identify factors predicting OS in patients with PS ≥2.ResultsThe numbers of patients with PS 0–1, 2, and 3–4 were 602, 98, and 55, respectively; the ORRs in these groups were 29.5, 15.3, and 9.1%, respectively, and the median OS times were 14.3, 3.1, and 2.4 months, respectively. In multivariate Cox regression analysis, a neutrophil–lymphocyte ratio (NLR) ≥3.5 (hazard ratio [HR] = 1.897) and liver metastasis (HR = 2.072) were associated with OS in the PS ≥2 subgroup. The median OS of patients with PS ≥2 without either risk factor was 6.8 months, compared with 3.1 months for patients with one risk factor and 2.3 months for patients with both risk factors.ConclusionsPS ≥2 portended worse ORR and OS than PS ≤1 despite a comparable safety profile. Among the patients with impaired PS, patients with NLR <3.5 and no liver metastasis may most greatly benefit from pembrolizumab therapy.

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“…The value of performance status in predicting mortality following ICI administration is supported by data from clinical trials of pembrolizumab, which show shorter OS in patients with NSCLC who have PS 2 rather than PS 0–1 [12, 13]. Real‐world analysis of patients who received ICI therapy close to end of life has also identified PS 3–4 as a poor prognostic factor [14, 15]. Nevertheless, Journal of the National Comprehensive Cancer Network guidelines currently recommend single‐agent pembrolizumab as first‐line therapy in patients with NSCLC who cannot tolerate platinum‐based chemotherapy [16].…”

Section: Discussionmentioning

confidence: 99%

Clinical Outcomes of Patients with Metastatic Cancer Receiving Immune Checkpoint Inhibitors in the Inpatient Setting

et al. 2020

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Background. As indications for immune checkpoint inhibitor (ICI) therapy have increased in recent years, so has the proportion of patients eligible for this type of therapy. However, a lack of data exists about the risks and benefits of ICI therapy in hospitalized patients, who tend to be frailer and sicker than patients enrolled in clinical trials. Material and methods. We conducted a retrospective cohort study among hospitalized patients with metastatic solid tumors who received ICI therapy at a large academic cancer center over the course of 4 years. We analyzed the characteristics and outcomes of these patients and identified demographic and clinical factors that could be used to predict mortality. Results. During the 4-year study period, 106 patients were treated with ICI therapy while admitted to the hospital; seventy (66%) had Eastern Cooperative Oncology Group (ECOG) Performance Status ≥2, which would have prevented them from enrolling in most clinical trials of ICIs. Fifty-two patients (49%) died either during admission or within 30 days of discharge; median overall survival was 1.0 month from discharge, and 16 patients (15%) were alive 6 months after discharge. Independent predictors of death following receipt of inpatient ICI included a diagnosis of non-small cell lung cancer relative to melanoma and prior treatment with two or more lines of therapy. Conclusion. The poor overall outcomes observed in this study may give clinicians pause when considering ICI therapy for hospitalized patients, particularly those with characteristics that are associated with a greater risk of mortality. The Oncologist 2020;9999:• • Implications for Practice: Immunotherapy strategies for cancer patients are rapidly evolving and their use is expanding, but not all patients will develop a response, and secondary toxicity can be significant and challenging. This is especially evident on hospitalized patients, where the economic cost derived from inpatient ICI administration is important and the clinical benefit is sometimes unclear. The poor overall outcomes evidenced in the ICI inpatient population in our study show the need to better identify the patients that will respond to these therapies, which will also help to decrease the financial burden imposed by these highly priced therapies.

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Immune Checkpoint Inhibitor Use Near the End of Life: A Single-Center Retrospective Study

Cited by 28 publications

References 6 publications

Performance status and end‐of‐life care among adults with non–small cell lung cancer receiving immune checkpoint inhibitors

Performance status and end‐of‐life care among adults with non–small cell lung cancer receiving immune checkpoint inhibitors

Pembrolizumab for treating advanced urothelial carcinoma in patients with impaired performance status: Analysis of a Japanese nationwide cohort

Clinical Outcomes of Patients with Metastatic Cancer Receiving Immune Checkpoint Inhibitors in the Inpatient Setting

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