Survival and quality-of-life outcomes in early-stage NSCLC patients: a literature review of real-world evidence.

Aim: Assess the long-term survival and quality-of-life outcomes in early-stage NSCLC (eNSCLC) patients. Methods: Review of long-term survival and quality-of-life after curative treatment in eNSCLC patients in observational studies. Results: Disease-free proportion decreased in stage III vs stage I patients. Recurrence-free proportion decreased with age and disease stage. Advanced stage and vascular invasion increased risk of late recurrence. Conditional 5-year relative survival rates did not exceed 87%, indicating higher mortality in eNSCLC survivors. Lower conditional survival rates and relative survival rates were associated with older age and advanced disease. Survivors of eNSCLC had poorer physical quality-of-life. Conclusion: Despite curative-intent therapy, survivors of eNSCLC still face significant risks of recurrence, excess mortality, and diminished quality-of-life.

Early-stage NSCLC (eNSCLC) encompassing stage I and II, and resectable stage III disease is initially managed with curative-intent surgery and adjuvant chemotherapy to reduce the risk of recurrence. However, understanding the true curative potential and long-term outcomes is crucial for optimal clinical management. A literature review was conducted to identify observational studies describing long-term survival and quality-of-life outcomes following curative intent therapy in patients with eNSCLC. The proportion of patients who remained disease-free over time (without recurrence or death) statistically significantly decreased in patients with stage III disease compared with stage I disease. Similarly, the proportion of patients who remained recurrence-free over time decreased with increasing age and disease stage. A considerable risk of late recurrence (recurrence five or more years following resection) remained, increasing with advanced stage and tumor characteristics such as vascular invasion. Conditional 5-year relative survival rates did not exceed 87% in any study, indicating higher rates of all-cause mortality in long-term survivors of eNSCLC compared with members of the general population of the same age. Lower conditional 5-year relative survival rates, and 5 and 10-year relative survival rates were associated with older age and higher pathologic stage. Compared with the general population, survivors of eNSCLC reported significantly poorer physical quality-of-life, suggesting that symptoms persist after treatment. Overall, real-world evidence suggests that after standard curative-intent therapy, survivors of eNSCLC may not be considered fully cured, indicating a need for more effective adjuvant treatment in addition to the current standard of care.

Treatment patterns and survival of patients with locoregional recurrence in early-stage NSCLC: a literature review of real-world evidence.

Approximately 10-50% of patients treated for early-stage (I-III), resectable non-small cell lung cancer (eNSCLC) will develop locoregional recurrence. There is a lack of prospective trials evaluating optimal post-surgery follow-up for this patient population, and treatment guidelines recommend salvage therapies such as surgery, local ablative therapy, and (chemo)radiotherapy. A literature review was conducted according to pre-defined criteria to identify observational studies describing treatment patterns and survival outcomes in patients with eNSCLC who experienced locoregional recurrence. Results showed that, in real-world clinical practice, around 80% of patients with locoregional recurrence underwent any form of active treatment. The most frequently administered treatments were chemotherapy (35.7%), chemoradiotherapy (31.2%), radiotherapy (20.3%), and surgery alone (12.8%). Chemoradiotherapy was associated with improved PFS and OS compared with radiotherapy, while no statistically significant survival benefits were observed for patients receiving surgery in addition to these treatments. The overall survival of patients following treatment for locoregional recurrence was generally poor, and the proportion of patients who experienced any form of post-treatment re-recurrence ranged from 35 to 72%. These findings highlight the need to develop more effective treatment strategies for locoregional recurrence, including preventative treatments, and strategies to improve the survival outcomes of those who do develop locoregional recurrence.

Systematic reviews of economic burden and health-related quality of life in patients with acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a rare hematologic malignancy largely affecting older adults. Comorbidities may compromise fitness and eligibility for high-intensity chemotherapy (HIC). This study presents the results of two systematic reviews (SRs) assessing (1) the impact of AML and current treatments on health-related quality of life (HRQoL), and (2) the economic burden and cost drivers of AML in patients who are ineligible for HIC. METHODS: Electronic searches (MEDLINE, EMBASE, EconLit, Cochrane library) were supplemented with manual searching of conference, utility, and HTA databases. All studies reporting HRQoL or economic data for patients with AML who were ineligible for HIC were included. RESULTS: The HRQoL SR included ten studies. Patients with AML have lower baseline HRQoL than other cancer patients or the general population, and those receiving lower intensity treatment have lower HRQoL than those eligible for HIC. Low baseline HRQoL predicts poor outcomes, and treatment had variable effects on HRQoL. The economic burden SR included nine studies. Medical costs varied widely, reflecting the heterogeneity of AML. Hospitalization is a key cost driver in AML treatment but was largely not considered in cost studies. Medical resource utilization comprised drug acquisition, drug administration, disease monitoring tests, transfusions, adverse event management, supportive care/monitoring costs and terminal care. CONCLUSION: As new drugs emerge that extend survival, assessment of HRQoL will be important to evaluate the quality of that survival. Cost data, driven by transfusions and hospitalization, will be important to evaluate the economic value of new treatments.

Early introduction of a semi-elemental formula may be cost saving compared to a polymeric formula among critically ill patients requiring enteral nutrition: a cohort cost-consequence model.

OBJECTIVES: Gastrointestinal (GI) intolerance is associated with adverse outcomes in critically ill patients receiving enteral nutrition (EN). The objective of this analysis is to quantify the cost of GI intolerance and the cost implications of starting with semi-elemental EN in intensive care units (ICUs). STUDY DESIGN: A US-based cost-consequence model was developed to compare the costs for patients with and without GI intolerance and the costs with semi-elemental or standard EN while varying the proportion of GI intolerance cases avoided. MATERIALS AND METHODS: ICU data on GI intolerance prevalence and outcomes in patients receiving EN were derived from an observational study. ICU stay costs were obtained from literature and the costs of EN from US customers' price lists. The model was used to conduct a threshold analysis, which calculated the minimum number of cases of GI intolerance that would have to be avoided to make the initial use of semi-elemental formula cost saving for the cohort. RESULTS: Out of 100 patients receiving EN, 31 had GI intolerance requiring a median ICU stay of 14.4 days versus 11.3 days for each patient without GI intolerance. The model calculated that semi-elemental formula was cost saving versus standard formula when only three cases of GI intolerance were prevented per 100 patients (7% of GI intolerance cases avoided). CONCLUSION: In the US setting, the model predicts that initial use of semi-elemental instead of standard EN can result in cost savings through the reduction in length of ICU stay if >7% of GI intolerance cases are avoided.

Review and comparison of clinical evidence submitted to support European Medicines Agency market authorization of orphan-designated oncological treatments.

BACKGROUND: Clinical trials for treatments indicated for orphan diseases may be limited due to the low prevalence of such diseases; this can result in implications for both regulatory and health economic perspectives. This study assessed the pivotal clinical evidence packages submitted to support applications for European Medicines Agency (EMA) marketing authorizations for treatments for orphan conditions, in relation to the size of the eligible patient population. METHODS: Approved treatments for EMA-designated orphan conditions (defined as life-threatening or chronically debilitating conditions that affect ≤5/10,000 people) were identified from the EMA web site. All treatments reviewed were included in anatomical therapeutic chemical (ATC) category L (antineoplastic and immunomodulating drugs): this category was selected because it is the largest ATC category, containing almost 50% of all approved orphan-designated products. Treatments were reviewed if they had been approved within the past 7 years and had been evaluated in a controlled trial using at least one survival-based clinical endpoint. Treatments were compared in terms of patient-years (accumulated duration of follow-up), the number of patients in the pivotal trials and disease prevalence. RESULTS: As of 1 February 2014, 68 treatments had been approved for orphan-designated conditions, of which 30 belonged to ATC category L and 14 met all inclusion criteria. The number of patients in the pivotal trials ranged from 162 to 846 (median 485). In terms of patient-years, the longest duration of follow-up was seen in the pivotal trial of mifamurtide in osteosarcoma, which had 4068 patient-years; excluding this trial, follow-up ranged from 308 to 2906 patient-years (median 1796 years). Osteosarcoma had the second smallest eligible patient population (0.5/10,000 persons) of the reviewed treatments. CONCLUSIONS: Clinical trials of orphan treatments are often limited by low patient numbers and inadequate follow-up. Pooling of expertise in single centres and the establishment of rare disease reference networks and patient registries may facilitate appropriate trial design for orphan-designated treatments. This analysis found that the pivotal clinical trial for mifamurtide in osteosarcoma had the largest number of patient-years of follow-up, despite a small eligible patient population, showing that it is possible to conduct studies with an adequate patient population size and duration of follow-up in patient-years, and a comparative design with clinical, survival-based, endpoints.

The impact of infusion reactions associated with monoclonal antibodies in metastatic colorectal cancer: a European perspective.

BACKGROUND AND OBJECTIVES: Published data on the clinical and economic impact of infusion reactions to monoclonal antibodies are limited. This study investigated oncologists' and oncology nurses' opinions about resource use associated with infusion reactions and the impact on patient management in Europe. METHODS: Eighty oncologists and nurses from Denmark, France, Germany, Greece, Italy, Spain, Sweden and the UK currently treating patients with metastatic colorectal cancer were interviewed by telephone using a 27-item questionnaire developed for this study. RESULTS: The mean estimated number of staff (physicians and nurses) involved in managing an infusion reaction was 1.97 for a grade 1, 2.35 for a grade 2, 3.6 for a grade 3 and 5.3 for a grade 4 reaction. In respondents' experiences, most patients with grade 3 infusion reactions (73.4%) were admitted to hospital for treatment; 82.5% of those with grade 4 infusion reactions were treated in intensive care. The estimated duration of hospital treatment was 13.3 ± 29 h for a grade 3 infusion reaction, increasing to 48.1 ± 43.7 h for a grade 4 infusion reaction. CONCLUSIONS: According to respondents, management of infusion reactions led to substantial resource use, which increased with the severity of the reaction. More severe reactions also led to anxiety in patients and distress to staff.