A cost-effectiveness analysis of avelumab plus best supportive care versus best supportive care alone as first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma in Taiwan.

BACKGROUND: Patients with locally advanced or metastatic urothelial carcinoma have limited treatment options and a poor prognosis. The JAVELIN Bladder 100 trial showed that avelumab as first-line maintenance plus best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with locally advanced or metastatic urothelial carcinoma that had not progressed with first-line platinum-containing chemotherapy. AIMS: We assessed whether avelumab plus best supportive care is a cost-effective treatment option versus best supportive care alone in this patient group in Taiwan. METHODS AND RESULTS: A partitioned survival model was used to estimate the costs and effects of avelumab plus best supportive care versus best supportive care alone over a 20-year time horizon from the perspective of Taiwan's National Health Insurance Administration. Patient-level data from JAVELIN Bladder 100 on efficacy, safety, utility, and time on treatment were analyzed to provide parameters for the model. Log-normal and Weibull distributions were used for overall survival and progression-free survival, respectively. Costs of healthcare resources, drug acquisition, adverse events, and progression were identified through publicly available data sources and clinician interviews. The model estimated total costs, life years, and quality-adjusted life years. In the modeled base case, avelumab plus best supportive care increased survival versus best supportive care alone by 0.79 life years (2.93 vs. 2.14) and 0.61 quality-adjusted life years (2.15 vs. 1.54). The incremental cost-effectiveness ratio for avelumab plus best supportive care versus best supportive care alone was NT$1 827 680. Most (78%) of the probabilistic sensitivity analyses fell below three times the gross domestic product per capita. Scenario analysis indicated that life year and quality-adjusted life year gains were most sensitive to alternative survival extrapolations for both avelumab plus best supportive care and best supportive care alone. CONCLUSION: Avelumab first-line maintenance therapy combined with best supportive care was determined as a cost-effective treatment strategy for patients in Taiwan diagnosed with locally advanced or metastatic urothelial carcinoma that had not progressed with platinum-containing chemotherapy.

Terminally Ill Cancer Patients' Concordance Between Preferred Life-Sustaining Treatment States in Their Last Six Months of Life and Received Life-Sustaining Treatment States in Their Last Month: An Observational Study.

CONTEXT/OBJECTIVE: The extent to which patients' preferences for end-of-life (EOL) care are honored may be distorted if preferences are measured long before death, a common approach of existing research. We examined the concordance between cancer patients' states of life-sustaining treatments (LSTs) received in their last month and LST preference states assessed longitudinally over their last six months. METHODS: We examined states of preferred and received LSTs (cardiopulmonary resuscitation, intensive care unit care, chest compression, intubation with mechanical ventilation, intravenous nutrition, and nasogastric tube feeding) in 271 cancer patients' last six months by a transition model with hidden Markov modeling (HMM). The extent of concordance was measured by a percentage and a kappa value. RESULTS: HMM identified four LST preference states: life-sustaining preferring, comfort preferring, uncertain, and nutrition preferring. HMM identified four LST states received in patients' last month: generally received LSTs, LSTs uniformly withheld, selectively received LSTs, and received intravenous nutrition only. LSTs received concurred poorly with patients' preferences estimated right before death (39.5% and kappa value: 0.06 [95% CI: -0.02, 0.13]). Patients in the life-sustaining-preferring, uncertain, and nutrition-preferring states primarily received no LSTs, and patients in three of four states received intravenous nutrition against their preferences. Concordance was strongest for comfort-preferring patients. CONCLUSIONS: Concordance was poor between patients' preferred and received LST states. Interventions are needed to clarify patients' EOL care goals and to facilitate their understanding about LST's ineffectiveness in prolonging life at EOL. Such interventions might increase patients' comfort preference and ensure concordance between their preferred and received EOL care.

Trajectory and predictors of quality of life during the dying process: roles of perceived sense of burden to others and posttraumatic growth.

PURPOSE: Quality of life (QOL) at end of life (EOL) is related to important themes, e.g., "sense of burden to others" and "perceived posttraumatic growth," which have never been investigated concurrently. The purposes of this study were: (1) to describe the trajectory of QOL during the dying process and (2) to identify determinants of QOL, including the roles of perceived sense of burden to others and posttraumatic growth. METHODS: A convenience sample of 313 terminally ill cancer patients was surveyed and longitudinally followed until death. QOL was measured by a modified McGill quality of life scale, and determinants were evaluated by a multiple linear regression model with the generalized estimating equation. RESULTS: Terminally ill Taiwanese cancer patients' QOL decreased substantially as their death approached. However, after controlling for confounders, patients' QOL did not change significantly in the last months of their life. QOL was significantly better for female and non-middle-aged patients with a religious affiliation of Buddhism/Taoism. Poorer QOL tended to be experienced by patients with greater physical symptom distress, anxiety, and depression. Patient QOL increased with greater tangible support, but decreased with greater emotional and affectionate social support. QOL was diminished by a greater degree of perceived burden to others but improved with greater perceived posttraumatic growth. CONCLUSIONS: Deteriorating QOL as death approaches may not be inevitable. Optimal QOL at EOL may be achieved by interventions designed to adequately manage physical and psychological symptoms, enhance social support, lighten perceived sense of burden to others, and facilitate experiences of posttraumatic growth.

Trajectories of the multidimensional dying experience for terminally ill cancer patients.

CONTEXT: Studies exploring the trajectories of physical-psychological-social-spiritual dying experiences frequently treat changes in these experiences as consistent across different domains and over time. OBJECTIVE: This prospective, longitudinal investigation was designed to characterize trajectories of the multidimensional dying experience for cancer patients in their last year of life. METHODS: Trajectories of physical-psychological-social-spiritual/existential dimensions and overall quality of life (QOL) were identified among 313 cancer patients using mixed-effects models to test for linear, quadratic, or cubic changes. Changes in each variable were evaluated for clinical significance using minimal important difference. RESULTS: When patients transitioned to their end of life, symptom distress, functional dependence, anxiety, and depressive symptoms slightly increased, followed by a stable status for approximately four to six months, and accelerated dramatically to the first clinically significant changes at three to four months before death. Perceived social support and post-traumatic growth declined gradually to clinically significant changes at one and four months before death, respectively. Perceived sense of burden to others increased steadily in the last year of life, with no clinically significant changes identified. Overall QOL deteriorated gradually in the last year but did not reach a clinically significant change until 2.5 months before death. CONCLUSION: All dimensions deteriorated in the last year of life but with distinctive physical-psychological-social-spiritual/existential and overall QOL trajectories. Recognizing trajectory patterns and tipping points of accelerating deterioration in each dimension can help clinicians anticipate times of increased distress, initiate timely, effective interventions to relieve patient suffering, and facilitate high-quality end-of-life care tailored to patients' needs and preferences.

Longitudinal changes and predictors of caregiving burden while providing end-of-life care for terminally ill cancer patients.

BACKGROUND: The effect of caring for a dying cancer patient on caregiving burden has been explored primarily in Western-based studies with small samples or in studies that did not follow up until the patient's death, but has not yet been investigated in Taiwan. OBJECTIVE: The study's goals were (1) to identify the trajectory of caregiving burden for family caregivers (FCs) of terminally ill cancer patients in Taiwan, and (2) to investigate the determinants of caregiving burden in a large sample and with longitudinal follow-ups, until the patient's death. METHOD: A prospective, longitudinal study was conducted among 193 FCs. The trajectory and determinants of caregiving burden were identified by a generalized estimation equation approach. RESULTS: Caregiving burden did not change as the patient's death approached. FCs experienced heavy caregiving burden when their relative suffered from greater symptom distress or if they were spousal caregivers; provided high intensity of assistance to the patient while spending fewer hours providing care; reported financial insufficiency; or had lower social support, fewer psychological resources, or less confidence in caregiving. CONCLUSIONS: Taiwanese family caregivers' carry moderate caregiving burden which did not change significantly as the patients' death approached. The effects of caregiving burden while providing EOL care to terminally ill cancer patients may be tempered substantially by enhancing family caregivers caregiving confidence, social support, and psychological resources.