Use of targeted therapy in cancer patients in the end-of-life period.

2014 ◽  
Vol 32 (31_suppl) ◽  
pp. 129-129
Author(s):  
Alysson Wann ◽  
David M. Ashley ◽  
Mustafa Khasraw
Keyword(s):  
Targeted Therapy ◽  
End Of Life ◽  
Targeted Therapies ◽  
Performance Status ◽  
Limited Data ◽  
Single Centre ◽  
Prior Therapy ◽  
End Of Treatment ◽  
Targeted Agent ◽  
Gender Type

129 Background: There is limited data on the use of these targeted therapies in patients at the end of life. This study reviews the pattern of use of targeted and potentially futile, toxic and costly therapies at the end of life at an Australian cancer centre. Methods: A retrospective single-centre review covering 12 month period of patients who died < 3 months of starting a targeted agent. We extracted demographics, types of cancers, types of therapy, median age and lines of prior therapy. Results: 478 patients were on targeted therapies during this period. 54 patients, (11.3%) died < 3 months. Of those, the median age was 69 years, men 65%, women 35%. 27 had haematological malignancies (mostly lymphoma and multiple myeloma), 21 had solid tumours (mostly colon and lung cancer). Ten agents were represented with erlotinib, bevacizumab, and rituximab having higher total number of deaths and none on transtuzumab. Treatment lines were first in 64.8%, second in 20.4% and 14.8% had > 2 lines of treatment. Performance status was only documented in 9.3% at start and 11.1% at end of treatment. Symptoms at the start of treatment that can be used to track improvement were only documented in 25 patients (46.3%). Gender, type of cancer, age was found to have no influence on death < 3 months of targeted treatment. Unfortunately we were unable to extract QoL data. Conclusions: In this small single centre descriptive study, the use of targeted therapy in the end of life population was common, mostly in first line treatment. No factors have shown correlation with dying < 3 months of targeted therapies. There is a need to better document performance status and QoL data and also to analyse indicators of when it is appropriate to cease targeted therapies.

Targeted agent use in patients with cancer at the end of life.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 215-215 ◽  
Author(s):  
David Hui ◽  
Meghan Sri Karuturi ◽  
Kimberson Cochien Tanco ◽  
Jung Hye Kwon ◽  
Sun Hyun Kim ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
End Of Life ◽  
Hematologic Malignancies ◽  
Poor Quality ◽  
Chemotherapeutic Agents ◽  
Concurrent Chemotherapy ◽  
Targeted Agents ◽  
Patients With Cancer ◽  
Lung Malignancies ◽  
Targeted Agent

215 Background: Chemotherapy use at the end of life is considered an indicator of poor quality of care. The use of targeted agent has not been well characterized. In this study, we determined the frequency and predictors of targeted therapy use in the last 30 days of life. Methods: All adult patients residing in the Houston area who died of advanced cancer between September 1, 2009 and February 28, 2010 and had contact with our institution within the last three months of life were included. We collected baseline demographics and data on chemotherapy and targeted agents. Results: 816 patients were included: average age 62 (range 21 to 97), female 48% and White 61%. The median interval between the last treatment and death was 47 (interquartile range 21 to 97) days for targeted agents and 57 (26 to 118) days for chemotherapeutic agents. 116 (14%) patients received targeted agents and 147 (18%) received chemotherapy within the last 30 days of life. 43 (5%) patients received targeted agents had concurrent chemotherapy. The most common targeted agents in the last 30 days of life were erlotinib (n=25), bevacizumab (n=20) and rituximab (n=11). In multivariate analysis, younger age, hematologic, and lung malignancies were associated with increased targeted agent use in the last 30 days of life (Table). Conclusions: Targeted agents were used as often as chemotherapy at the end of life, particularly among younger patients and those with hematologic malignancies. Guidelines on targeted therapy use at the end of life are needed. [Table: see text]

scholarly journals Palliative care in the context of immune and targeted therapies: A qualitative study of bereaved carers’ experiences in metastatic melanoma

2020 ◽  
Vol 34 (10) ◽  
pp. 1351-1360 ◽  
Author(s):  
Jennifer A Fox ◽  
John Rosenberg ◽  
Stuart Ekberg ◽  
Danette Langbecker
Keyword(s):  
Palliative Care ◽  
Targeted Therapy ◽  
Qualitative Study ◽  
Metastatic Melanoma ◽  
End Of Life ◽  
Targeted Therapies ◽  
Treatment Options ◽  
Family Needs ◽  
Term Survival ◽  
Treatment Paradigm

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.

Single agent immunotherapy for relapsed or refractory small cell lung cancer (rrSCLC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20094-e20094
Author(s):  
Ankur Singh ◽  
Tamjeed Ahmed ◽  
Andy Dothard ◽  
Stefan C. Grant ◽  
Jimmy Ruiz ◽  
...  
Keyword(s):  
End Of Life ◽  
Performance Status ◽  
Treatment Options ◽  
Single Agent ◽  
Life Outcomes ◽  
Small Cell Lung ◽  
Prior Therapy ◽  
Primary Endpoints ◽  
Reversible Encephalopathy ◽  
Poor Efficacy

e20094 Background: There are limited effective treatment options for rrSCLC. Based on results from CheckMate 032 (n = 98) and KEYNOTE-158 (n = 107), both of which were limited to performance status (PS) 0-1, guidelines recommend consideration of single agent PD-1 immunotherapy (IO) for patients (pts) with PS 0-2. Methods: All rrSCLC pts receiving single agent IO at our institution from May 2016 – April 2018 were retrospectively analyzed with IRB approval. Primary endpoints were overall survival (OS) and end-of-life outcomes. Results: 48 rrSCLC pts who were predominantly PS 2-3 (56%), female (63%), and Caucasian (90%) received single agent IO with either nivolumab (94%) or pembrolizumab (6%) for either relapsed (81%) or refractory (19%; defined as initial diagnosis < 180 days) SCLC. They received median 3 cycles (IQR 2-5). 32 deaths occurred during the analysis period. 6 and 12 month (mo) OS were 31% and 18%, as compared to 45% and 33% reported in CheckMate, respectively. Adverse events (AEs) leading to treatment discontinuation occurred in 5 (10%) and serious AEs (pneumonitis and posterior reversible encephalopathy syndrome) occurred in 2 (4%). For end-of-life outcomes, 18 (38%) were referred to hospice at any point, 8 (17%) began IO within 30 days of death, and 7 (15%) received a dose of IO within 14 days of death. The subgroup of pts who received ≥2 prior lines of therapy appear to have had greater benefit. Conclusions: Although tolerable, salvage single agent IO for rrSCLC in these unselected pts had poor efficacy and may have led to under-utilization of end-of-life resources. It may still be beneficial among pts with more indolent, treatment-responsive disease, as indicated by multiple lines of prior therapy. But overall, these results support the combination of IO with chemotherapy or novel agent as part of a clinical trial. Further investigation is warranted to better define its use in this setting. [Table: see text]

Etoposide dosage adjustment in two patients with neuroendocrine tumors and severe liver impairment

2019 ◽  
Vol 26 (2) ◽  
pp. 500-506
Author(s):  
Ola Mashni ◽  
Khlood Qasem ◽  
Aseel Abu Sara ◽  
Wedad Awad
Keyword(s):  
Neuroendocrine Tumors ◽  
Performance Status ◽  
Close Monitoring ◽  
Limited Data ◽  
Severe Liver ◽  
Liver Impairment ◽  
End Of Treatment ◽  
Platinum Based Chemotherapy ◽  
Dosing Strategies ◽  
Tomography Scan

Introduction Limited data are available on dosing etoposide in patients with liver impairment. Case report We report the dosing strategies for etoposide utilized in two patients with neuroendocrine tumors and severe liver impairment. Management and outcomes Treatment consisted of platinum-based chemotherapy regimens, with the decision of whether to administer etoposide and at what doses being based on the liver function before each chemotherapy cycle. By the end of treatment, total bilirubin was normal, and the performance status of both patients had improved, with stable computed tomography scan findings. Discussion The reported two cases suggest that the administration of etoposide at reduced doses with close monitoring in patients with neuroendocrine tumors and severe liver impairment may still be considered as an option and may improve outcomes.

Treatment of metastatic renal cancer with high-dose interleukin-2 after targeted therapy.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 439-439 ◽  
Author(s):  
Robert E. Hawkins ◽  
Victoria Galvis ◽  
Jonathan Shanks ◽  
Neha Dalal ◽  
Fiona Thistlethwaite ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Complete Remission ◽  
Renal Cancer ◽  
Targeted Therapies ◽  
Interleukin 2 ◽  
High Dose ◽  
Consolidation Therapy ◽  
First Line ◽  
Metastatic Renal Cancer ◽  
Targeted Agent

439 Background: High-Dose Interleukin-2 (HD IL2) remains a good option for treatment of metastatic renal cancer. As a first-line treatment, in carefully selected patients, it can produce high rates of response ( OR 50%; CR 25%) (Shablak A et al., J Immunotherapy 2011, 34(1):107-122). Its use after targeted therapies is controversial and there are reports of increased toxicity, particularly an increased incidence of cardiovascular toxicity (and possibly a reduced response rate (Cho DC et al., J Immunotherapy 2009, 32(2):181-520). However, there is potential to use it either in patients who have failed treatment with targeted therapy or as a consolidation therapy after successful treatment with a targeted agent. Methods: Here we present the outcomes of 16 patients treated with first-line immunotherapy with HD-IL2 after targeted therapy: of these 8 had been treated after failure of 1-3 lines of targeted therapy and 8 have been treated as consolidation after initial response to sunitinib. The histological characteristics of the tumours all fitted into the “favourable” group as defined previously by us and all had high levels of expression of CAIX (> 80%). All had ECOG PS 0/1, a satisfactory baseline stress echo, an interval of at least 8 weeks from last dose of targeted agent to start of HD-IL2 and at most 2 organs of disease. Results: Toxicity is indistinguishable from that of patients without prior treatment and no patient needed inotropic support or admission to intensive care. The number of doses given per cycle was also similar to that in unpretreated patients. Overall the response rates are excellent – with 9/13 evaluable patients having RECIST defined response and 6/13 having a complete remission. To date none of the patients in complete remission have realpsed but follow up is relatively short with the longest being 24 months. The responses have been particularly striking following treatment with mTor inhibitors. Conclusions: Overall, HD IL2 can be given safely in carefully selected patients after targeted therapies. It appears to be effective as a salvage therapy and potentially as a consolidation therapy. Updated results will be presented.

scholarly journals Chemotherapy and Targeted Therapy Near the end of life Affects Aggressiveness of Palliative Care

2020 ◽  
Author(s):  
Wen-Wu Cheng ◽  
Zhe Zhang ◽  
Meng-Lei Chen ◽  
Xiao-Li Gu
Keyword(s):  
Targeted Therapy ◽  
Cardiopulmonary Resuscitation ◽  
End Of Life ◽  
Palliative Chemotherapy ◽  
Metastatic Cancer ◽  
Performance Status ◽  
Cancer Center ◽  
Integrated Therapy ◽  
The Difference ◽  
To Receive

Abstract Background: In patients with advanced cancer, considering the increased application of targeted therapy and immunotherapies, we explored the difference between indicators of chemotherapy and targeted therapy in the last month of life.Methods: Electronic medical data of patients who died from metastatic cancer and received targeted therapy and palliative chemotherapy from April 2007 to December 2018 at the Department of Integrated Therapy, Fudan University Shanghai Cancer Center were analyzed retrospectively. To determine those variables that were judged to be independent predictors of the use of palliative chemotherapy and targeted therapy, and the differences between them, univariate and multivariate analyses were used.Results: Of the 585 patients included in the study, 87 (14.9%) received palliative chemotherapy and 125 (21.3%) underwent targeted therapy during the last month. Patients who received continued chemotherapy within the last month were subjected to more intensive treatment (admitted to an intensive care unit (ICU) in the last month of life (OR, 2.33; CI [1.91–2.92], P < 0.001), and received cardiopulmonary resuscitation(OR, 4.18; CI [2.91–5.40],P < 0.001)), than those who did not. Analysis of subgroups showed that the lung cancer was independently associated with targeted therapy, and admission to an ICU was independently associated with palliative chemotherapy.Conclusions: Younger patients without complications and with better performance status were more likely to receive chemotherapy. Lower rates of cardiopulmonary resuscitation and admission to ICU correlated with receipt of targeted therapy at the end of life compared with those who received chemotherapy in the last 30 days.

scholarly journals Platform study of genotyping-guided precision medicine for rare solid tumours: a study protocol for a phase II, non-randomised, 18-month, open-label, multiarm, single-centre clinical trial testing the safety and efficacy of multiple Chinese-approved targeted drugs and PD-1 inhibitors in the treatment of metastatic rare tumours

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e044543
Author(s):  
Shuhang Wang ◽  
Hui-Yao Huang ◽  
Dawei Wu ◽  
Hong Fang ◽  
Jianming Ying ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Targeted Therapy ◽  
Single Agent ◽  
Solid Tumours ◽  
Targeted Drugs ◽  
Gene Fusions ◽  
Single Centre ◽  
Open Label ◽  
Safety And Efficacy ◽  
Rare Tumours

IntroductionLimited clinical studies have been conducted on rare solid tumours, and there are few guidelines on the diagnosis and treatment, including experiences with targeted therapy and immunotherapy, of rare solid tumours in China, resulting in limited treatment options and poor outcomes. This study first proposes a definition of rare tumours and is designed to test the preliminary efficacy of targeted and immunotherapy drugs for the treatment of rare tumours.Methods and analysisThis is a phase II, open-label, non-randomised, multiarm, single-centre clinical trial in patients with advanced rare solid tumours who failed standard treatment; the study aims to evaluate the safety and efficacy of targeted drugs in patients with advanced rare solid tumours with corresponding actionable alterations, as well as the safety and efficacy of immune checkpoint (programmed death receptor inhibitor 1, PD-1) inhibitors in patients with advanced rare solid tumours without actionable alterations. Patients with advanced rare tumours who fail standardised treatment and carry actionable alterations (Epidermal growth factor receptor (EGFR) mutations, ALK gene fusions, ROS-1 gene fusions, C-MET gene amplifications/mutations, BRAF mutations, CDKN2A mutations, BRCA1/2 mutations, HER-2 mutations/overexpressions/amplifications or C-KIT mutations) will be enrolled in the targeted therapy arm and be given the corresponding targeted drugs. Patients without actionable alterations will be enrolled in the PD-1 inhibitor arm and be treated with sintilimab. After the patients treated with vemurafenib, niraparib and palbociclib acquire resistance, they will receive combination treatment with sintilimab or atezolizumab. With the use of Simon’s two-stage Minimax design, and the sample size was estimated to be 770. The primary endpoint of this study is the objective response rate. The secondary endpoints are progression-free survival in the targeted treatment group and single-agent immunotherapy group; the duration of response in the targeted therapy and single-agent immunotherapy groups; durable clinical benefit in the single-agent immunotherapy group; and the incidence of adverse events.Ethics and disseminationEthics approval was obtained from the Chinese Academy of Medical Sciences (ID: 20/132-2328). The results from this study will be actively disseminated through manuscript publications and conference presentations.Trial registration numbersNCT04423185; ChiCTR2000039310.

scholarly journals SURG-05. IDEAL TREATMENT REGIMEN FOR PATIENTS WITH ≥1 BRAIN METASTASIS FROM PRIMARY NON-SMALL-CELL LUNG CANCER – A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii204-ii204
Author(s):  
Karanbir Brar ◽  
Yosef Ellenbogen ◽  
Behnam Sadeghirad ◽  
Jiawen Deng ◽  
Winston Hou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Targeted Therapies ◽  
Meta Analysis ◽  
Performance Status ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
China National Knowledge Infrastructure

Abstract BACKGROUND Brain metastases (BM) are common in non-small cell lung cancer (NSCLC). The aim of this study was to assess the comparative effectiveness of treatments for BM from NSCLC. METHODS We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published until October 2018. We also searched the Chinese databases Wanfang Data, Wanfang Med Online, China National Knowledge Infrastructure, and Chongqing VIP Information for RCTs published until September 2019. Trials including &gt; 10 patients were selected. The primary outcomes were overall survival (OS) and intracranial progression-free survival (PFS). We used a frequentist random-effects model for network meta-analysis and assessed the certainty of evidence using the GRADE approach. RESULTS Among 8798 abstracts, 106 RCTs (9452 patients) met inclusion criteria. Median sample size was 67 (range 25-554). All trials included adult patients with histologically proven NSCLC and &gt;1 BM proven on CT/MRI. Of trials that reported performance status (e.g. ECOG or KPS, n=67), 63/67 excluded patients with non-favorable performance status. Interventions assessed included surgery, WBRT, SRS, targeted therapies (i.e. EGFR/ALK inhibitors), and chemotherapy. Compared to WBRT alone, several interventions demonstrated a statistically significant increase in median OS, including non-targeted chemotherapy + surgery (MD: 415.3 days, 95% CI: 31.3-799.4), WBRT + EGFRi (MD: 200.2 days, 95% CI:146.3-254.1), and EGFRi alone (MD: 169.7 days, 95% CI: 49.7-289.7). Among all interventions, only WBRT + EGFRi showed a significant improvement in median PFS (MD: 108.0 days, 95%CI: 48.5-167.5). CONCLUSIONS Our preliminary analyses indicate an OS and PFS benefit on the addition of EGFR inhibitors to WBRT for the treatment of BMs from NSCLC. Further analyses of hazard ratios for OS/PFS are underway, and subgroup analyses are planned. These data support the growing role of targeted therapies in the treatment of BMs, particularly in susceptible mutant tumours.

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