Background/Objective
Facilitating death preparedness is important for improving cancer patients' quality of death and dying. We aimed to identify factors associated with the four death‐preparedness ...states (no‐preparedness, cognitive‐only, emotional‐only, and sufficient‐preparedness) focusing on modifiable factors.
Methods
In this cohort study, we identified factors associated with 314 Taiwanese cancer patients' death‐preparedness states from time‐invariant socio‐demographics and lagged time‐varying modifiable variables, including disease burden, physician prognostic disclosure, patient‐family communication on end‐of‐life (EOL) issues, and perceived social support using hierarchical generalized linear modeling.
Results
Patients who were male, older, without financial hardship to make ends meet, and suffered lower symptom distress were more likely to be in the emotional‐only and sufficient‐preparedness states than the no‐death‐preparedness‐state. Younger age (adjusted odds ratio 95% confidence interval = 0.95 0.91, 0.99 per year increase in age) and greater functional dependency (1.05 1.00, 1.11) were associated with being in the cognitive‐only state. Physician prognostic disclosure increased the likelihood of being in the cognitive‐only (51.51 14.01, 189.36) and sufficient‐preparedness (47.42 10.93, 205.79) states, whereas higher patient‐family communication on EOL issues reduced likelihood for the emotional‐only state (0.38 0.21, 0.69). Higher perceived social support reduced the likelihood of cognitive‐only (0.94 0.91, 0.98) but increased the chance of emotional‐only (1.09 1.05, 1.14) state membership.
Conclusions
Death‐preparedness states are associated with patients' socio‐demographics, disease burden, physician prognostic disclosure, patient‐family communication on EOL issues, and perceived social support. Providing accurate prognostic disclosure, adequately managing symptom distress, supporting those with higher functional dependence, promoting empathetic patient‐family communication on EOL issues, and enhancing perceived social support may facilitate death preparedness.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Objective
Death preparedness involves cognitive prognostic awareness and emotional acceptance of a relative's death. Effects of retrospectively assessed cognitive prognostic awareness and emotional ...preparedness for patient death have been individually investigated among bereaved family caregivers. We aimed to prospectively examine associations of caregivers' death‐preparedness states, determined by conjoint cognitive prognostic awareness and emotional preparedness for death, with bereavement outcomes.
Methods
Associations of caregivers' death‐preparedness states (no‐death‐preparedness, cognitive‐death‐preparedness‐only, emotional‐death‐preparedness‐only, and sufficient‐death‐preparedness states) at last preloss assessment with bereavement outcomes over the first two bereavement years were evaluated among 332 caregivers of advanced cancer patients using hierarchical linear models with the logit‐transformed posterior probability for each death‐preparedness state.
Results
Caregivers with a higher logit‐transformed posterior probability for sufficient death‐preparedness state reported less prolonged‐grief symptoms, lower likelihoods of severe depressive symptoms and heightened decisional regret, and better mental health‐related quality of life (HRQOL). Caregivers with a higher logit‐transformed posterior probability for no‐death‐preparedness state reported less prolonged‐grief symptoms, a lower likelihood of severe depressive symptoms, and better mental HRQOL. A higher logit‐transformed posterior probability for cognitive‐death‐preparedness‐only state was associated with bereaved caregivers' higher likelihood of heightened decisional regret, whereas that for emotional‐death‐preparedness‐only state was not associated with caregivers' bereavement outcomes.
Conclusions
Caregivers' bereavement outcomes were associated with their preloss death‐preparedness states, except for physical health‐related QOL. Interventions focused on not only cultivating caregivers' accurate prognostic awareness but also adequately preparing them emotionally for their relative's forthcoming death are actionable opportunities for high‐quality end‐of‐life care and are urgently warranted to facilitate caregivers' bereavement adjustment.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Objective
Preparing family surrogates for patient death and end‐of‐life (EOL) decision making may reduce surrogate decisional conflict and regret. Preparedness for patient death involves cognitive ...and emotional preparedness. We assessed the associations of surrogates' death‐preparedness states (that integrate both cognitive and emotional preparedness for patient death) with surrogates' decisional conflict and regret.
Methods
Associations of 173 surrogates' death‐preparedness states (no, cognitive‐only, emotional‐only, and sufficient preparedness states) with decisional conflict (measured by the Decision Conflict Scale) and heightened decisional regret (Decision Regret Scale scores >25) were evaluated using hierarchical linear modeling and hierarchical generalized linear modeling, respectively, during a longitudinal observational study at a medical center over cancer patients' last 6 months.
Results
Surrogates reported high decisional conflict (mean standard deviation = 41.48 6.05), and 52.7% of assessments exceeded the threshold for heightened decisional regret. Surrogates in the cognitive‐only preparedness state reported a significantly higher level of decisional conflict (β = 3.010 95% CI = 1.124, 4.896) than those in the sufficient preparedness state. Surrogates in the no (adjusted odds ratio AOR 95% CI = 0.293 0.113, 0.733) and emotional‐only (AOR 95% CI = 0.359 0.149, 0.866) preparedness states were less likely to suffer heightened decisional regret than those in the sufficient preparedness state.
Conclusions
Surrogates' decisional conflict and heightened decisional regret are associated with their death‐preparedness states. Improving emotional preparedness for the patient's death among surrogates in the cognitive‐only preparedness state and meeting the specific needs of those in the no, emotional‐only, and sufficient preparedness states are actionable high‐quality EOL‐care interventions that may lessen decisional conflict and decisional regret.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Terminally ill cancer patients do not engage in end-of-life (EOL) care discussions or do so only when death is imminent, despite guidelines for EOL care discussions early in their disease trajectory. ...Most studies on patient-reported EOL care discussions are cross sectional without exploring the evolution of EOL care discussions as death approaches. Cross-sectional studies cannot determine the direction of association between EOL care discussions and patients' prognostic awareness, psychological well-being, and quality of life (QOL).
We examined the evolution and associations of accurate prognostic awareness, functional dependence, physical and psychological symptom distress, and QOL with patient-physician EOL care discussions among 256 terminally ill cancer patients in their last six months by hierarchical generalized linear modeling with logistic regression and by arranging time-varying modifiable variables and EOL care discussions in a distinct time sequence.
The prevalence of physician-patient EOL care discussions increased as death approached (9.2%, 11.8%, and 18.3% for 91–180, 31–90, and 1–30 days before death, respectively) but only reached significance in the last month. Accurate prognostic awareness facilitated subsequent physician-patient EOL care discussions, whereas better patient-reported QOL and more anxiety symptoms hindered such discussions. The likelihood of EOL care discussions was not associated with levels of physical symptom distress, functional dependence, or depressive symptoms.
Physician-patient EOL care discussions for terminally ill Taiwanese cancer patients remain uncommon even when death approaches. Physicians should facilitate EOL care discussions by cultivating patients' accurate prognostic awareness early in their cancer trajectory when they are physically and psychologically competent, with better QOL, thus promoting informed and value-based EOL care decision making.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BackgroundThe programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) axis plays a central role in suppressing antitumor immunity; axis dysregulation can be used by cancer cells to evade ...the immune system. Tislelizumab, an investigational monoclonal antibody with high affinity and binding specificity for PD-1, was engineered to minimize binding to FcγR on macrophages to limit antibody-dependent phagocytosis, a potential mechanism of resistance to anti-PD-1 therapy. The aim of this phase IA/IB study was to investigate the safety/tolerability, antitumor effects and optimal dose and schedule of tislelizumab in patients with advanced solid tumors.MethodsPatients (aged ≥18 years) enrolled in phase IA received intravenous tislelizumab 0.5, 2, 5 or 10 mg/kg every 2 weeks; 2 or 5 mg/kg administered every 2 weeks or every 3 weeks; or 200 mg every 3 weeks; patients in phase IB received 5 mg/kg every 3 weeks. Primary objectives were to assess tislelizumab’s safety/tolerability profile by adverse event (AE) monitoring and antitumor activity using RECIST V.1.1. PD-L1 expression was assessed retrospectively with the VENTANA PD-L1 (SP263) Assay.ResultsBetween May 2015 and October 2017, 451 patients (n=116, IA; n=335, IB) were enrolled. Fatigue (28%), nausea (25%) and decreased appetite (20%) were the most commonly reported AEs. Most AEs were grade 1–2 severity; anemia (4.9%) was the most common grade 3–4 AE. Treatment-related AEs led to discontinuation in 5.3% of patients. Grade 5 AEs were reported in 14 patients; 2 were considered related to tislelizumab. Pneumonitis (2%) and colitis (1%) were the most common serious tislelizumab-related AEs. As of May 2019, 18% of patients achieved a confirmed objective response in phase IA and 12% in phase IB; median follow-up duration was 13.6 and 7.6 months, respectively. Pharmacokinetics, safety and antitumor activity obtained from both phase IA and IB determined the tislelizumab recommended dose; ultimately, tislelizumab 200 mg intravenous every 3 weeks was the dose and schedule recommended to be taken into subsequent clinical trials.ConclusionsTislelizumab monotherapy demonstrated an acceptable safety/tolerability profile. Durable responses were observed in heavily pretreated patients with advanced solid tumors, supporting the evaluation of tislelizumab 200 mg every 3 weeks, as monotherapy and in combination therapy, for the treatment of solid tumors and hematological malignancies.Trial registration number NCT02407990.
Aim and Objectives
This study explored the effect of transdermal buprenorphine on quality of life and six symptoms in cancer patients with pain.
Background
Transdermal opioids offer advantages over ...traditional routes of administration. The impact of transdermal buprenorphine on quality of life for patients with cancer in Asian populations is unknown.
Design
This study employed a single‐arm observational repeated measures design. Cancer patients with pain were evaluated prior to treatment (baseline). Over a 4‐week treatment period, quality of life and symptoms were assessed at 2 and 4 weeks. This study adhered to the recommendations of STROBE guidelines.
Methods
This multi‐site study was conducted in six hospitals located across northern, middle and southern Taiwan. Adult cancer patients whose pain was previously stable with opioid analgesics and, based on clinical judgement, were able to convert to transdermal buprenorphine treatment were invited to participate. Quality of life was measured with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ‐C30).
Results
Generalised estimating equations showed participants who completed at least one follow‐up measurement (N = 80) over 4‐weeks had a significant improvement in overall quality of life. Functional status only improved for social functioning. However, symptom severity decreased significantly for nausea/vomiting, pain, insomnia and constipation.
Conclusions
The study provides initial evidence supporting transdermal buprenorphine for providing beneficial effects of improving quality of life and reducing severity of symptoms in Asian patients with cancer.
Relevance to clinical practice
The findings of this study can inform the clinical practice that the use of transdermal buprenorphine in cancer patients with pain may also reduce the severity of other symptoms and improve overall quality of life.
Trial registration details
This study was registered in ClinicalTrials.gov. Identifier: NCT04315831.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Summary
Purpose
This study aimed to evaluate the safety and pharmacokinetic (PK) profiles of HLX07, a novel, recombinant, humanized anti-epidermal growth factor receptor (EGFR) antibody, in patients ...with advanced solid cancers who had failed standard therapy or for whom no standard therapy was available.
Methods
In this prospective, open-label, Phase I dose escalation study, patients aged ≥18 years (≥20 years for patients in Taiwan) with histologically-confirmed metastatic or recurrent epithelial carcinoma that had no
K-RAS
or
B-RAF
mutations were enrolled in a ‘3 + 3’ escalation design. HLX07 was administered weekly by 2-h intravenous infusion at doses ranging from 50 to 800 mg. The primary endpoint was summary listing of participants reporting treatment-emergent adverse events (TEAEs). Secondary endpoints included PK analysis, serum anti-HLX07 antibody assessments and efficacy.
Results
In total, 19 patients were enrolled between 1 October 2016 and 16 July 2019 to receive HLX07 at doses of 50 (n = 3), 100 (n = 3), 200 (n = 3), 400 (n = 3), 600 (n = 3) and 800 (n = 4) mg per week. All patients experienced at least one TEAE, most commonly fatigue (68.4%), nausea (47.4%), paronychia (31.6%) and vomiting (31.6%). Serious TEAEs were reported in 11 patients but only one serious TEAE (dyspnea in 600 mg cohort) was regarded as possibly related to study treatment. No dose limiting toxicity (DLT) was reported. Systemic exposure to HLX07 increased proportionally with dose. Anti-HLX07 antibodies were not detected in any patients.
Conclusion
HLX07 was well tolerated (at dose levels up to 800 mg/week) and promising in patients with advanced solid cancers.
Clinical Trial Registration
: The study was registered at
ClinicalTrials.gov
: NCT02648490 (Jan 7, 2016).
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This cohort study investigated factors associated with 336 Taiwanese family caregivers' emotional and cognitive preparedness for death of a loved one with terminal cancer. Caregivers' ...death-preparedness states (no-death-preparedness as reference, cognitive-death-preparedness-only, emotional-death-preparedness-only, and sufficient-death-preparedness states) were previously identified. Associations of factors with these states were determined by a hierarchical generalized linear model. Financial hardship decreased caregivers' likelihood for the emotional-death-preparedness-only and sufficient-death-preparedness states. Physician prognostic disclosure increased membership in the cognitive-death-preparedness-only and sufficient-death-preparedness states. The better the quality of the patient-caregiver relationship, the higher the odds for the emotional-death-preparedness-only and sufficient-death-preparedness states, whereas the greater the tendency for caregivers to communicate end-of-life issues with their loved one, the lower the odds for emotional-death-preparedness-only state membership. Stronger coping capacity increased membership in the emotional-death-preparedness-only state, but perceived social support was not associated with state membership. Providing effective interventions tailored to at-risk family caregivers' specific needs may facilitate their death preparedness.
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BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
Background
Patients with esophageal squamous cell carcinoma (SCC) have limited treatment options. Blocking transforming growth factor-β (TGFβ), which can be overexpressed in these tumors, may enhance ...responses to programmed cell death protein 1/programmed death-ligand 1 PD-(L)1 inhibitors. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGFβ receptor II (TGFβRII) (a TGFβ “trap”) fused to a human IgG1 monoclonal antibody blocking PD-L1.
Objective
The objective of this study was to investigate the safety and efficacy of bintrafusp alfa in Asian patients with pretreated, PD-L1–unselected esophageal SCC.
Patients and Methods
In a phase 1 study, Asian patients with pretreated esophageal SCC received bintrafusp alfa 1200 mg every 2 weeks until disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was safety/tolerability with a goal of exploring clinical activity.
Results
By the database cutoff of August 24, 2018, 30 patients (76.7% had two or more prior anticancer regimens) received bintrafusp alfa for a median of 6.1 weeks; two remained on treatment. Nineteen patients (63.3%) had treatment-related adverse events, seven (23.3%) with grade 3/4 events, and there were no treatment-related deaths. The confirmed objective response rate (ORR) per independent review was 10.0% (95% confidence interval CI 2.1–26.5); responses lasted 2.8–8.3 + months. All responses occurred in immune-excluded tumors. Investigator-assessed confirmed ORR was 20.0% (95% CI 7.7–38.6). Median overall survival was 11.9 months (95% CI 5.7–not reached).
Conclusions
Bintrafusp alfa demonstrated a manageable safety profile and efficacy in Asian patients with pretreated esophageal SCC.
Clinical Trials Registration
NCT02699515.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular ...carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC. Methods: The multiregional phase 2 study RATIONALE-208 examined single-agent tislelizumab (200 mg intravenously every 3 weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by the Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab. Results: Between April 9, 2018, and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% (n = 32/249; 95% confidence interval CI, 9–18), including five complete and 27 partial responses. The number of prior lines of therapy did not impact ORR (one prior line, 13% 95% CI, 8–20; two or more prior lines, 13% 95% CI, 7–20). Median duration of response was not reached. The disease control rate was 53%, and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment. Conclusion: Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC.
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