End-of-life care and immune checkpoint inhibitors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11531-11531
Author(s):  
Hazel O'Sullivan ◽  
Dearbhaile Collins ◽  
Deirdre O'Mahony ◽  
Derek Power ◽  
Richard Bambury ◽  
...  

11531 Background: In the era of cytotoxic chemotherapy, aggressive cancer treatment and hospitalization at the end of life (EOL) has been associated with a worse quality of death. Meanwhile, in the era of immunotherapy (IO), little is known of the impact of these novel agents on EOL care. The aim of this study was to evaluate the EOL care of metastatic cancer patients treated with immune checkpoint inhibitors. Methods: We conducted a retrospective analysis of patients prescribedPD1/L1 or CTLA-4 antibodies in Cork University Hospital (CUH) and Mercy University Hospital (MUH) between January 2013 to December 2018. Patients treated on a clinical trial were excluded. Results: We identified 224 patients treated with immune checkpoint inhibitors (outside of a clinical trial) in CUH and MUH over the described 6 year period. 108 of these patients were deceased, 102 electronic files were available for analysis. Of the 102 patients, 57 had metastatic melanoma, 33 non small cell lung cancer, 8 renal cell carcinoma, 4 had other advanced malignancies. 43% were female and 57% were male. 6% of patients had an ECOG performance status (PS) of 0 at diagnosis, 80% PS of 1 and 10% PS of 2. Median age at death was 62 years. 47 patients were treated with pembrolizumab, 26 nivolumab, 25 ipilimumab, 2 nivolumab/ipilimumab and 2 received atezolizumab. 29 patients received IO as first line treatment, 50 as second line, 17 as third line and 6 as fourth line. Median number of IO cycles received was 4 (range 1 - 41). Progression of disease (62%) and declining performance status (14%) were the most common reasons for discontinuation of IO treatment. 16 of the 102 patients received a further line of systemic therapy. Median time from last dose of IO to death was 57 days. 20 patients (20%) died within 30 days of last dose of IO. Of these 20 patients, the median number of cycles of IO received was 2 (range 1-7), 8 of these 20 patients received one cycle of IO only. 39 patients (38%) attended the ED in the last month of life. 47 (46%) patients had at least one hospital admission in the last month of life, the median hospital length of stay was 6 days (range 1-30) and 22 patients died in hospital. 94% of patients were referred to palliative care, the median time from palliative care referral to death was 64 days (range 1- 1010), 62% of patients died in hospice. Conclusions: Patients with advanced cancer treated with immunotherapy have high rates of hospital admissions and ED attendances despite early palliative care involvement. 20% of patients died within 30 days of IO. More research is needed to help physicians identify patients who are least likely to benefit from IO so as not to treat futile cases.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17112-e17112
Author(s):  
Lydia Glick ◽  
Cassra Clark ◽  
Timothy M. Han ◽  
James Ryan Mark ◽  
Leonard G. Gomella ◽  
...  

e17112 Background: Immune Checkpoint Inhibitors (ICI) are increasingly utilized for genitourinary (GU) malignancies. However, data is lacking on the efficacy of these drugs in “real-world” populations - patients who do not fit the strict clinical trial criteria, but may still benefit from therapy. We performed a retrospective analysis of patients receiving ICI at a single tertiary-care institution, with special attention to clinical trial enrollment, adverse events, progression and survival. Methods: Patients receiving ICI for GU malignancies at Thomas Jefferson University Hospital from January 2017 to January 2019 were identified. Descriptive statistics of treatment and pathologies were performed. Progression-free survival (PFS) was calculated from start of ICI to documentation of progression or last follow-up. PFS and overall survival were assessed using Kaplan Meier log-rank test, stratified by trial enrollment. Results: 111 patients were included: 37 on ICI clinical trial, 70 received ICI “off-trial” and 4 received ICI in both settings. 11 patients (10%) underwent multiple courses of ICI throughout treatment. The number of patients initiating ICI increased annually; by 2018, the number of patients initiated on ICI “off-trial” exceeded those initiating ICI “on-trial” (79% vs 21%). Treated pathology included Urothelial Carcinoma (UC; 42%), Renal Cell Carcinoma (RCC; 28%), and Prostate Adenocarcinoma (PCa; 20%). “Off-trial” ICI was more often administered later in the disease course, compared to a more even distribution of “on-trial” ICI administration. Mean PFS and OS for both cohorts can be seen in Table. Conclusions: As seen in our single-institution referral center, the use of immune checkpoint inhibitors has significantly increased – and is now more commonly used off-trial than on-trial. As their use becomes more common, their efficacy in “off-trial” populations must be further investigated. [Table: see text]


2020 ◽  
Vol 8 (1) ◽  
pp. e000144 ◽  
Author(s):  
Sarah Abou Alaiwi ◽  
Wanling Xie ◽  
Amin H Nassar ◽  
Shaan Dudani ◽  
Dylan Martini ◽  
...  

BackgroundImmune checkpoint inhibitors (ICI) induce a range of immune-related adverse events (irAEs) with various degrees of severity. While clinical experience with ICI retreatment following clinically significant irAEs is growing, the safety and efficacy are not yet well characterized.MethodsThis multicenter retrospective study identified patients with metastatic renal cell carcinoma treated with ICI who had >1 week therapy interruption for irAEs. Patients were classified into retreatment and discontinuation cohorts based on whether or not they resumed an ICI. Toxicity and clinical outcomes were assessed descriptively.ResultsOf 499 patients treated with ICIs, 80 developed irAEs warranting treatment interruption; 36 (45%) of whom were restarted on an ICI and 44 (55%) who permanently discontinued. Median time to initial irAE was similar between the retreatment and discontinuation cohorts (2.8 vs 2.7 months, p=0.59). The type and grade of irAEs were balanced across the cohorts; however, fewer retreatment patients required corticosteroids (55.6% vs 84.1%, p=0.007) and hospitalizations (33.3% vs 65.9%, p=0.007) for irAE management compared with discontinuation patients. Median treatment holiday before reinitiation was 0.9 months (0.2–31.6). After retreatment, 50% (n=18/36) experienced subsequent irAEs (12 new, 6 recurrent) with 7 (19%) grade 3 events and 13 drug interruptions. Median time to irAE recurrence after retreatment was 2.8 months (range: 0.3–13.8). Retreatment resulted in 6 (23.1%) additional responses in 26 patients whose disease had not previously responded. From first ICI initiation, median time to next therapy was 14.2 months (95% CI 8.2 to 18.9) and 9.0 months (5.3 to 25.8), and 2-year overall survival was 76% (95%CI 55% to 88%) and 66% (48% to 79%) in the retreatment and discontinuation groups, respectively.ConclusionsDespite a considerable rate of irAE recurrence with retreatment after a prior clinically significant irAE, most irAEs were low grade and controllable. Prospective studies are warranted to confirm that retreatment enhances survival outcomes that justify the safety risks.


2019 ◽  
Vol 37 (3) ◽  
pp. 179-184 ◽  
Author(s):  
Chad Glisch ◽  
Yuya Hagiwara ◽  
Stephanie Gilbertson-White ◽  
Yubo Gao ◽  
Laurel Lyckholm

Background: Immune checkpoint inhibitors have changed the landscape of cancer care by increasing progression-free and overall survival in some patients with cancer. We evaluated use and variables contributing to immune checkpoint inhibitor treatment near the end of life. Methods: We studied 157 patients who received immune checkpoint inhibitors and died between January 2015 and December 2018. All patients had a palliative care consult any time between starting an immune checkpoint inhibitor and death. Univariate and multivariate models were used to examine variables related to immune checkpoint inhibitor use near the end of life. Results: Among 157 patients studied, 42 (27%) received a dose of immune checkpoint inhibitor in the last 30 days of life. Those who received treatment in the last 30 days of life had lower hospice enrollment (19 [45%] vs 78 [69%], P = .007) and higher rates of dying in the hospital (23 [56%] vs 33 [29%], P = .002). The percentage of patients with Eastern Cooperative Oncology Group (ECOG) ≥3 at the time of last immune checkpoint inhibitor dose was higher in the group that received immune checkpoint inhibitor treatment in the last 30 days of life (11 [26%] vs 9 [8%], P = .003). Lack of traditional chemotherapy after immune checkpoint inhibitor, ECOG ≥3, and lack of hospice enrollment were independently associated with receiving immune checkpoint inhibitor in the last 30 days of life. Conclusion: Immune checkpoint inhibitor use in the last 30 days of life is common and associated with poor performance status, lower hospice enrollment, and dying in the hospital.


2021 ◽  
Vol 13 (2) ◽  
Author(s):  
Elisa Lucchini ◽  
Chiara Rusconi ◽  
Mario Levis ◽  
Francesca Ricci ◽  
Armando Santoro ◽  
...  

The rate of complete remission (CR) with the anti-PD1 immune checkpoint inhibitors (ICI) nivolumab (N) and pembrolizumab (P) in patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) is low (20-30%), and the majority of patients eventually relapse. One strategy to improve their outcome is to combine ICI with radiotherapy (ICI-RT), taking advantage of a supposed synergistic effect. We retrospectively collected data of 12 adult patients with R/R cHL treated with ICI-RT delivered during or within 8 weeks from the start or after the end of ICI. Median age at ICI-RT was 37 years, 50% had previously received an autologous stem cell transplantation (SCT) and 92% brentuximab vedotin. RT was given concurrently, before or after ICI in 4, 1 and 7 patients. Median RT dose was 30Gy, for a median duration of 22 days. Median number of ICI administrations was 15. Overall response and CR rate were 100% and 58%. Nine patients received subsequent SCT consolidation (7 allogeneic and 2 autologous). After a median follow-up of 18 months, 92% of patients were in CR. No major concerns about safety were reported. ICI-RT combination appears to be a feasible and highly active bridge treatment to transplant consolidation.


2018 ◽  
Vol 17 (12) ◽  
pp. 854-855 ◽  
Author(s):  
Jun Tang ◽  
Jia Xin Yu ◽  
Vanessa M. Hubbard-Lucey ◽  
Svetoslav T. Neftelinov ◽  
Jeffrey P. Hodge ◽  
...  

2020 ◽  
Vol 50 (12) ◽  
pp. 1447-1453
Author(s):  
Toshio Kubo ◽  
Hiromi Watanabe ◽  
Kiichiro Ninomiya ◽  
Kenichiro Kudo ◽  
Daisuke Minami ◽  
...  

Abstract Objectives Immune checkpoint inhibitors offer longer survival than chemotherapy in several clinical trials for advanced non-small cell lung cancer. In subset analyses of clinical trials, immune checkpoint inhibitors extended survival in patients aged ≥65 years, but the effects in patients aged ≥75 years are controversial. We performed multicenter, collaborative and retrospective analyses of immune checkpoint inhibitor efficacy and safety in non-small cell lung cancer patients aged ≥75 years. Methods We retrospectively studied 434 advanced non-small cell lung cancer patients who received immune checkpoint inhibitors from December 2015 to December 2017, and retrospectively applied the Geriatric (G) 8 screening tool with medical records. Results Of the 434 patients who received immune checkpoint inhibitors, 100 were aged ≥75 years. Five patients with performance status 3 were omitted from the final analysis. Immune checkpoint inhibitors were given as a first-line treatment to 20 patients. The objective response rates, median progression-free survival rates and median survival times were 35.0%, 6.1 months and 10.7 months for first-line treatment, and 20.0%, 2.9 months and 14.7 months for second- or later-line treatments, respectively. The median modified G8 score was 11.0. The median survival time was longer in the high modified G8 (≥12.0) group than in the low modified G8 (≤11.0) group (18.7 vs. 8.7 months; P = 0.02). Likewise, the median survival time was 15.5 months (performance status 0–1) vs. 3.2 months (performance status 2) (P < 0.01). The grade ≥ 2 immune-related adverse events incidence was 36.8%. Conclusions In this study, immune checkpoint inhibitors were effective and tolerable for patients aged ≥75 years. The modified G8 screening tool and performance status were associated with the outcome of older non-small cell lung cancer patients treated with immune checkpoint inhibitors.


2018 ◽  
Vol 23 (12) ◽  
pp. 1494-1499 ◽  
Author(s):  
Monica Khunger ◽  
Sagar Rakshit ◽  
Adrian V. Hernandez ◽  
Vinay Pasupuleti ◽  
Kate Glass ◽  
...  

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