The most common cause of mortality due to malignant neoplasms in the general population around the world is lung cancer. In the last 10 years, there has been an enormous improvement in the treatment of this disease, mainly due to the immunotherapy that activates the immune system to fight cancer. Patients with metastatic non-small cell lung cancer are a special group of patients requiring not only cancer treatment but also considerable support in the treatment of cancer-related problems, as well as comorbidities. Early palliative care is important in this area. In addition, there is certain evidence that medicines most commonly administered in palliative care may lower the efficacy of immunotherapy. The present review article compares information on the prolonging of life after early hospice care, which has become the foundation of current standards of management in patients with metastatic lung cancer, and reports of decreased efficacy of the immunotherapy due to the administration of major palliative care medications.
Objective: Antitumour treatment in the last 2 weeks of death (ATT-W2) and a new regimen of ATT within 30 days of death (NATT-M1) are considered as aggressive end-of-life (EOL) care. We aimed to assess factors associated with inappropriate use of antitumour treatment (ATT) at EOL.
Methods: Data of patients with cancer who died in 2013, 2015, 2017 and 2019 in a single for-profit cancer centre were retrospectively analysed. ATT was divided into chemotherapy (CT), oral targeted therapy (OTT), hormonotherapy and immunotherapy (IMT).
Results: A total of 1282 patients were included. NATT-M1 was given to 197 (15.37%) patients, and 167 (13.03%) had an ATT-W2. Patients with a performance status of <2 and treated with CT had more both ATT- W2 (OR=2.45, 95% CI 1.65 to 3.65, and OR=10.29, 95% CI 4.70 to 22.6, respectively) and NATT-M1 (OR=2.01, 95% CI 1.40 to 2.90, and OR=8.41, 95% CI 4.46 to 15.86). Predictive factors of a higher rate of ATT-W2 were treatment with OTT (OR=19.08, 95% CI 7.12 to 51.07), follow-up by a medical oncologist (OR=1.49, 95% CI 1.03 to 2.17), miscellaneous cancer (OR=3.50, 95% CI 1.13 to 10.85) and length of hospital stay before death of <13 days (OR=1.92, 95% CI 1.32 to 2.79). Urinary tract and male genital cancers received less ATT-W2 (OR=0.38, 95% CI 0.16 to 0.89, and OR=0.40, 95% CI 0.16 to 0.99) and patients treated by IMT or with age <69 years more NATT-M1 (OR=19.21, 95% CI 7.55 to 48.8, and OR=1.69, 95% CI 1.20 to 2.37). Patients followed up by the palliative care team (PCT) had fewer ATT-W2 and NATT-M1 (OR=0.49, 95% CI 0.35 to 0.71, and OR=0.42, 95% CI 0.30 to 0.58).
Conclusions: Most recent ATT and access to a PCT follow-up are the two most important potentially modifiable factors associated with aggressive EOL in patients with cancer. Early integrated palliative oncology care could help to decrease futile ATT at EOL.
Immunotherapy using one's own T cells that are genetically engineered to express a chimeric antigen receptor (CAR) is an emerging therapy for hematologic and non-hematologic cancer. CAR T cell therapy has induced rapid and durable clinical responses in otherwise fatal cancers, but is associated with unique, possibly severe, toxicities. This Fast Facts discusses the basics of CAR T cell therapy for clinicians, approved indications, and toxicities.
Lung cancer is one of the main causes of cancer-related mortality worldwide. Over the years, different therapeutic modalities have been adopted depending on tumor stage and patient characteristics, such as surgery, radiotherapy (RT), and chemotherapy. Recently, with the development of immune-checkpoint inhibitors (ICI), the treatment of metastatic and locally advanced non-small cell lung cancer (NSCLC) has experienced a revolution that has resulted in a significant improvement in overall survival with an enhanced toxicity profile. Despite this paradigm shift, most patients present some kind of resistance to ICI. In this setting, current research is shifting towards the integration of multiple therapies, with RT and ICI being one of the most promising based on the potential immunostimulatory synergy of this combination. This review gives an overview of the evolution and current state of the combination of RT and ICI and provides evidence-based data that can improve patient selection. The combination in lung cancer is a safe therapeutic approach that improves local control and progression-free survival, and it has the potential to unleash abscopal responses. Additionally, this treatment strategy seems to be able to re-sensitize select patients that have reached a state of resistance to ICI, further enabling the continuation of systemic therapy.
BACKGROUND: Immune and targeted therapies continue to transform treatment outcomes for those with metastatic melanoma. However, the role of palliative care within this treatment paradigm is not well understood.
AIM: To explore bereaved carers' experiences of immune and targeted therapy treatment options towards end of life for patients with metastatic melanoma.
DESIGN: An interpretive, qualitative study using a social constructivist framework was utilised. Interviews were recorded, transcribed and analysed using grounded theory methods.
SETTING/PARTICIPANTS: Participants (n = 20) were bereaved carers of patients who had received some form of immune and/or targeted therapy at one of three Australian metropolitan melanoma treatment centres.
RESULTS: Carers struggled to reconcile the positive discourse around the success of immune and targeted therapies in achieving long-term disease control, and the underlying uncertainty in predicting individual responses to therapy. Expectations that immune and targeted therapies necessarily provide longer-term survival were evident. Difficulty in prognostication due to clinical uncertainty and a desire to maintain hope resulted in lack of preparedness for treatment failure and end of life.
CONCLUSION: Immune and targeted therapies have resulted in increased prognostic challenges. There is a need to engage, educate and support patients and carers to prepare and plan amid these challenges. Educational initiatives must focus on improving communication between patients, carers and clinicians; the differences between palliative and end-of-life care; and increased competency of clinicians in having goals-of-care discussions. Clinicians must recognise and communicate the benefit of collaborative palliative care to meet patient and family needs holistically and comprehensively.
BACKGROUND: The purpose of this study was to investigate whether combining pembrolizumab with palliative radiation therapy (RT) improves outcomes in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC).
PATIENTS AND METHODS: Eligible patients had HR +/human epidermal growth factor receptor 2-negative MBC; were candidates for RT to = 1 bone, soft tissue, or lymph node lesion; and had = 1 lesion outside the RT field. Patients received 200 mg pembrolizumab intravenously 2 to 7 days prior to RT and on day 1 of repeating 21-day cycles. RT was delivered to a previously unirradiated area in 5 treatments each of 4 Gy. The primary endpoint was objective response rate. The study used a 2-stage design: 8 women were enrolled into the first stage, and if at least 1 of 8 patients experienced an objective response, 19 more would be enrolled. Secondary endpoints included progression-free survival, overall survival, and safety. Exploratory endpoints included association of overall response rate with programmed death-ligand 1 status and tumor-infiltrating lymphocytes.
RESULTS: Eight patients were enrolled in stage 1. The median age was 59 years, and the median prior lines of chemotherapy for metastatic disease was 2. There were no objective responses, and the study was closed to further accrual. The median progression-free survival was 1.4 months (95% confidence interval, 0.4-2.1 months), and the median overall survival was 2.9 months (95% confidence interval, 0.9-3.6 months). All-cause adverse events occurred in 87.5% of patients, including just 1 grade 3 event (elevation of aspartate aminotransferase).
CONCLUSIONS: RT combined with pembrolizumab did not produce an objective response in patients with heavily pre-treated HR+ MBC. Future studies should consider alternative radiation dosing and fractionation in patients with less heavily pre-treated HR+ MBC.
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-of-life 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.
Background: The therapeutic landscape in medical oncology continues to expand significantly. Newer therapies, especially immunotherapy, offer the hope of profound and durable responses with more tolerable side effect profiles. Integrating this information into the decision making process is challenging for patients and oncologists. Systemic anticancer treatment within the last thirty days of life is a key quality of care indicator and is one parameter used in the assessment of aggressiveness of care.
Methods: A retrospective review of medical records of all patients previously treated at Goulburn Valley Health oncology department who died between 1 January 2015 and 30 June 2018 was conducted. Information collected related to patient demographics, diagnosis, treatment, and hospital care within the last 30 days of life. These results were presented to the cancer services meeting and a quality improvement intervention program was instituted. A second retrospective review of medical records of all patients who died between 1 July 2018 and 31 December 2018 was conducted in order to measure the effect of this intervention.
Results: The initial audit period comprised 440 patients. 120 patients (27%) received treatment within the last 30 days of life. The re-audit period comprised 75 patients. 19 patients (25%) received treatment within the last 30 days of life. Treatment rates of chemotherapy reduced after the intervention in contrast to treatment rates of immunotherapy which increased. A separate analysis calculated the rate of mortality within 30 days of chemotherapy from the total number of patients who received chemotherapy was initially 8% and 2% in the re-audit period. Treatment within the last 30 days of life was associated with higher use of aggressive care such as emergency department presentation, hospitalisation, ICU admission and late hospice referral. Palliative care referral rates improved after the intervention.
Conclusion: This audit demonstrated that a quality improvement intervention can impact quality of care indicators with reductions in the use of chemotherapy within the last 30 days of life. However, immunotherapy use increased which may be explained by increased access and a better risk benefit balance.
In the present study, the influence of purely palliative radiotherapy (pRT) on the outcomes of patients with advanced cancer undergoing immune checkpoint blockade was evaluated. Patients were stratified into three groups: Patients who had received pRT within 6 months prior to the initiation of immunotherapy (previous pRT); patients who received pRT during immunotherapy (concurrent pRT); and patients who did not receive RT prior to or during immunotherapy (no RT group), and these groups were compared. The median overall survival (mOS), median progression free survival (mPFS) and median time-to-treatment failure (mTTF) for the previous pRT group were significantly shorter compared with the no RT group (mOS, 3.6 vs. 12.1 months, respectively, P=0.0095; mPFS 1.8 vs. 5.4 months, respectively, P=0.0016; mTTF 1.8 vs. 5.7 months, respectively, P=0.0035). The concurrent pRT group had a longer mTTF compared with the previous pRT group and similar outcomes to the no RT group. In the previous pRT group, 26.9% of the patients experienced immune-related adverse events compared with 40.1% of patients in the no RT group. Despite the use of pRT during immunotherapy being considered safe, the results of the present study suggest that pRT has a negative effect on immune balance.
Background: Immune checkpoint inhibitors (ICIs) have revolutionized treatment for many patients with advanced cancer. Little is known about ICI use near the end of life.
Objective: To describe ICI use near the end of life.
Design: Retrospective study of patients who received ICIs and died.
Setting/Subjects: Patients treated with ICIs who died between August 2014 and December 2018 (N = 441) at the University of Iowa.
Measurements: Comparisons were made between patients who received ICIs =30 days versus patients who received ICIs >30 days before death. The same analysis was done using a cutoff of 90 days.
Results: Two hundred ninety-four (67%) patients received ICIs in the last 90 days of life and 117 (27%) patients received ICIs in the last 30 days of life. Patients who received ICIs in the last 30 days of life received fewer mean doses and more often =3 total doses. They also had higher mean Eastern Cooperative Oncology Group (ECOG) scores, more patients with ECOG =3, higher rates of dying in the hospital, and lower hospice enrollment. Patients treated with ICIs in the last 90 days of life received fewer doses, more often =3 total doses, had a higher mean ECOG score, more patients with ECOG =3, and lower hospice enrollment. $7.1 million USD was spent on ICI medications in the last 90 days of life.
Conclusion: ICI use near the end of life is associated with poor performance status, lower hospice enrollment, dying in the hospital, financial toxicity, and minimal clinical benefit.
PURPOSE: Immunotherapy has rapidly become the mainstream treatment of multiple cancer types. Since the first drug approval in 2011, we have noted a decline in referrals from inpatient oncology to hospice and an increase in referrals to subacute rehabilitation (SAR) facilities, possibly with the aim of getting strong enough for immunotherapy and other promising drugs. This study explores outcomes after discharge to SAR, including rates of cancer-directed therapy after SAR, overall survival, and hospice use.
METHODS: We performed an electronic chart review of patients discharged from our inpatient oncology units to SAR facilities from 2009 to 2017. Demographics, admission statistics, and post-discharge outcomes were gathered from discharge summaries and targeted chart searches.
RESULTS: Three hundred fifty-eight patients were referred to SAR 413 times. One hundred seventy-four patients (49%) returned to the oncology clinic before readmission or death, and only 117 (33%) ever received additional cancer-directed treatment (chemotherapy, radiation, or immunotherapy). Among all discharges, 28% led to readmissions within 30 days. Seventy-four patients (21%) were deceased within 30 days, only 31% of whom were referred to hospice. Palliative care involvement resulted in more frequent do not resuscitate code status, documented goals of care discussions, and electronic advance directives.
CONCLUSION: A growing number of oncology inpatients are being discharged to SAR, but two thirds do not receive additional cancer therapy at any point, including a substantial fraction who are readmitted or deceased within 1 month. These data can help guide decision making and hospital discharge planning that aligns with patients' goals of care. More clinical data are needed to predict who is most likely to benefit from SAR and proceed to further cancer therapy.
Checkpoint immunotherapy is a rapidly evolving treatment paradigm for solid organ cancers. These medications are often antibodies that target key regulators of the immune system to unleash an immune system attack on cancer cells. Examples include cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors (e.g., ipilimumab) or programmed death receptor-1 (PD-1) inhibitors (e.g., pembrolizumab and nivolumab). See Fast Fact #277 for more information. Although heightened immune response against the tumor cells is intended, healthy tissues can also be attacked leading to unintended inflammation of almost any organ system. This has led to a unique set of immune-related adverse events (IRAEs). Given the expanding use of checkpoint immunotherapy, clinical awareness of IRAEs is important among generalist and palliative care clinicians.
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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.
Metastatic renal cell carcinoma (RCC) is a leading cause of cancer deaths in developed nations. The past decade has seen the approval of numerous systemic therapies for RCC, most recently immune checkpoint inhibitors (ICI). Nivolumab, an anti-programmed cell death 1 antibody, was superior to everolimus in a large phase 3 trial in clear-cell RCC (ccRCC), and is now approved by the US Food and Drug Administration for metastatic RCC after progression on prior anti-antiangiogenic therapy. The overall response rate is 25%, and there is a subset of patients who demonstrate pseudoprogression where initial tumor growth is followed by decreased tumor burden. Differentiating between progression and pseudoprogression has been chanllenging.
Herein we report the case of a patient with metastatic ccRCC with clinical deterioration and progression after 3 doses of nivolumab who went to hospice, only to come back 6 months later with less disease.
Purpose: Baseline use of corticosteroids is associated with poor outcomes in patients with non-small-cell lung cancer (NSCLC) treated with programmed cell death-1 axis inhibition. To approach the question of causation versus correlation for this association, we examined outcomes in patients treated with immunotherapy depending on whether corticosteroids were administered for cancer-related palliative reasons or cancer-unrelated indications.
Patients and methods: Clinical outcomes in patients with NSCLC treated with immunotherapy who received >= 10 mg prednisone were compared with outcomes in patients who received 0 to < 10 mg of prednisone.
RESULTS: Of 650 patients, the 93 patients (14.3%) who received >= 10 mg of prednisone at the time of immunotherapy initiation had shorter median progression-free survival (mPFS) and median overall survival (mOS) times than patients who received 0 to < 10 mg of prednisone (mPFS, 2.0 v 3.4 months, respectively; P = .01; mOS, 4.9 v 11.2 months, respectively; P < .001). When analyzed by reason for corticosteroid administration, mPFS and mOS were significantly shorter only among patients who received >= 10 mg prednisone for palliative indications compared with patients who received >= 10 mg prednisone for cancer-unrelated reasons and with patients receiving 0 to < 10 mg of prednisone (mPFS, 1.4 v 4.6 v 3.4 months, respectively; log-rank P < .001 across the three groups; mOS, 2.2 v 10.7 v 11.2 months, respectively; log-rank P < .001 across the three groups). There was no significant difference in mPFS or mOS in patients receiving >= 10 mg of prednisone for cancer-unrelated indications compared with patients receiving 0 to < 10 mg of prednisone.
CONCLUSION: Although patients with NSCLC treated with >= 10 mg of prednisone at the time of immunotherapy initiation have worse outcomes than patients who received 0 to < 10 mg of prednisone, this difference seems to be driven by a poor-prognosis subgroup of patients who receive corticosteroids for palliative indications.
Patients with cancer face an ever-changing landscape of tumor-directed therapies available to improve quality of life and potentially increase survival. The most recent advances, immunotherapeutics, offer a novel way to target cancer cells by engaging the body's own immune system. Using an expert panel of oncologists, palliative medicine physicians, and dual-trained specialists, we discuss current immunotherapies and their clinical uses, potential side effects and management strategies, and the implications of these newer treatments on goals of care conversations and care coordination. We aim to further engage palliative care specialists in the active care of cancer patients receiving immunotherapeutics and use a "Top 10" tips format to concisely present practical learning points to busy clinicians.
Background: Antiprogrammed death-1 antibodies (anti-PD1) have response rates of 40% in metastatic melanoma. Patients with poor performance status (PS) were excluded from clinical trials, yet use of anti-PD1 is widespread in clinical practice. Literature regarding clinical and palliative care outcomes in patients with poor PS treated with anti-PD1 is lacking.
Methods: Retrospective review of outcomes for all patients with advanced melanoma treated with anti-PD1 between 2012 and June 2015 at Peter MacCallum Cancer Centre, a tertiary specialist cancer center in Australia.
Results: Between 2012 and 2015, 91 patients received anti-PD1: median age 63, 65% males, 77% elevated LDH>1xULN (37/48 patients). Fifty-eight patients had baseline ECOG PS of 0-1 (64%), 24 patients ECOG PS 2-3 (26%) and ECOG PS was not recorded in nine patients (10%). Median overall survival (OS) for the ECOG PS 0-1 group was 19.5 months and 1.8 months for ECOG PS 2-3 (HR 5.5; 95% CI, 9.1-50.3; P = 0.0001). Tumor response was 23/58 (39%) in ECOG PS 0-1, 2/16 (12%) in ECOG PS 2 and 0/8 in ECOG PS 3. Toxicity did not differ between different groups. ECOG PS 2-3 patients were more likely to be treated and hospitalized within the last month of life compared to ECOG PS 0-1 patients, RR 1.75 (95% CI, 1.04-2.56, P = 0.019) and RR 1.73 (95% CI, 1.10-2.16, P = 0.009), respectively. ECOG PS 2-3 patients were more likely to die in an acute hospital RR 2.68 (95% CI, 1.17-6.51, P = 0.016).
Conclusions: Patients with poor baseline PS have a significantly lower OS and reduced response to anti-PD1. Further quality of life and palliative care research is needed.
Indépendamment de la tumeur primitive, le développement d'une ascite maligne réduit considérablement la qualité de vie dans ses aspects physiques, psychologiques et socioprofessionnels. A ce stade de la maladie, le traitement a pour objectif de soulager l'inconfort généré par le volume de l'épanchement liquidien. Ce travail, basé sur une synthèse de la littérature, passe en revue les moyens mis en oeuvre pour la prise en charge de ces malades. Il révèle que si l'ascite est le plus souvent réfractaire au traitement diurétique classique, de nouvelles techniques de drainage et surtout une immunothérapie ciblée se sont développées ces dernières années pour améliorer significativement la qualité de fin de vie.
Ce guide de référence est destiné aux personnes atteintes d'un mélanome de la peau. Il répond concrètement aux questions concernant les différents traitements proposés, la vie quotidienne, les démarches administratives. Il permet de faciliter les échanges avec les professionnels.