Cost Effectiveness of Nivolumab in Patients with Advanced, Previously Treated Squamous and Non-squamous Non-small-cell Lung Cancer in England.

OBJECTIVE: The aim of this study was to investigate the cost effectiveness of nivolumab versus docetaxel in previously treated, advanced non-small-cell lung cancer (NSCLC) in England and assess how conditional reimbursement within the Cancer Drugs Fund (CDF) can be used to ensure timely patient access to effective treatments. METHODS: Cost-effectiveness models developed for the National Institute for Health and Care Excellence (NICE) TA483 (squamous) and TA484 (non-squamous) technology appraisals were supplemented with updated overall survival (OS), progression-free survival (PFS), and time-to-treatment discontinuation data collected as part of the CDF data collection agreement. Both models were developed by using a partitioned-survival approach based on PFS and OS predictions from CheckMate 017 and CheckMate 057 to estimate the projected proportion of patients in each health state (progression free, progression, death) throughout the model's time horizon. The primary outcomes were estimated costs, quality-adjusted life-years (QALYs), and the resulting incremental cost-effectiveness ratio (ICER) expressed as cost/QALY gained. RESULTS: Base-case ICERs for treating patients with nivolumab versus docetaxel were £35,657/QALY and £38,703/QALY for squamous and non-squamous NSCLC patients, respectively, which are substantially lower than those obtained from what were deemed to be the most appropriate analyses for decision making in the original submissions when run with the same patient access scheme discount: £68,576/QALY and £73,189/QALY gained for squamous and non-squamous NSCLC, respectively. CONCLUSIONS: Nivolumab versus docetaxel is cost effective for treating locally advanced/metastatic NSCLC after prior chemotherapy in adults, regardless of tumour histology or programmed death-ligand 1 expression status.

Humanistic and cost burden of systemic sclerosis: A review of the literature.

BACKGROUND: Systemic sclerosis (SSc), or systemic scleroderma, is a chronic multisystem autoimmune disease characterised by widespread vascular injury and progressive fibrosis of the skin and internal organs. Patients with SSc have decreased survival, with pulmonary involvement as the main cause of death. Current treatments for SSc manage a range of symptoms but not the cause of the disease. Our review describes the humanistic and cost burden of SSc. METHODS: A structured review of the literature was conducted, using predefined search strategies to search PubMed, Embase, and the Cochrane Library. Grey literature searches also were conducted. RESULTS: In total, 2226 articles were identified in the databases and 52 were included; an additional 10 sources were included from the grey literature. The review identified six studies reporting relevant cost estimates conducted in five different countries and four studies that assessed the humanistic burden of SSc. Total direct annual medical costs per patient for Europe varied from €3544 to €8452. For Canada, these costs were reported to be from Can$5038 to Can$10,673. In the United States, the total direct health care costs were reported to be US$17,365 to US$18,396. Different key drivers of direct costs were reported, including hospitalisations, outpatients, and medication. The total annual costs per patient were reported at Can$18,453 in Canada and varied from €11,074 to €22,459 in Europe. Indirect costs represented the largest component of the total costs. EQ-5D utility scores were lower for patients with SSc than those observed in the general population, with reported mean values of 0.49 and 0.68, respectively. The average value of the Health Assessment Questionnaire for patients with SSc was significantly higher than the control population (0.94), and the average value of the SF-36 was significantly lower than the control population: 49.99 for the physical dimension and 58.42 for the mental dimension. CONCLUSIONS: Overall, there is a paucity of information on the burden of SSc. Nonetheless, our review indicates that the quality of life of patients with SSc is considerably lower than that of the general population. In addition, SSc places a considerable economic burden on health care systems and society as a whole.

Comparison of palbociclib in combination with letrozole or fulvestrant with endocrine therapies for advanced/metastatic breast cancer: network meta-analysis.

BACKGROUND: Palbociclib is the first cyclin-dependent kinase 4/6 inhibitor approved in the United States for HR+/HER2- advanced/metastatic breast cancer, in combination with letrozole as initial endocrine-based therapy in postmenopausal women or with fulvestrant in women with disease progression following endocrine therapy. We compared progression-free survival (PFS) and discontinuations due to adverse events for palbociclib combinations against other endocrine therapies using a mixed-treatment comparison meta-analysis of randomized, controlled trials. METHODS: A systematic literature review identified relevant trials. Separate analyses were conducted for each palbociclib combination using a Bayesian approach. Treatment rankings were established using the surface under the cumulative ranking curve (SUCRA). RESULTS: Sixty-five unique studies met inclusion criteria. Palbociclib plus letrozole had the highest SUCRA value (99.9%) and was associated with significantly longer PFS than all comparators in treatment-naïve patients (hazard ratios [HRs] ranged from 0.41 to 0.58). Palbociclib plus fulvestrant had the second highest SUCRA value (93.9%) and, in previously treated patients, yielded significantly longer PFS than most comparators (HRs ranged from 0.26 to 0.46); the exception was everolimus plus exemestane, with similar PFS (HR, 1.04; 95% credible interval [CrI], 0.58-1.76). Palbociclib plus fulvestrant was associated with significantly lower odds of discontinuation due to adverse events than everolimus plus exemestane (odds ratio, 0.14; 95% CrI, 0.05-0.39). CONCLUSIONS: The results suggest that the two palbociclib combinations yielded significantly greater PFS than endocrine therapy in treatment-naïve and previously treated patients with advanced/metastatic breast cancer. Palbociclib plus fulvestrant was associated with significantly less toxicity than everolimus plus exemestane.

Systematic Review with Network Meta-Analysis: Comparative Efficacy of Biologics in the Treatment of Moderately to Severely Active Ulcerative Colitis.

BACKGROUND: Biological therapies are increasingly used to treat ulcerative colitis (UC). AIM: To compare the efficacy of biologics in adults with moderately-to-severely active UC, stratified by prior exposure to anti-tumour necrosis factor (anti-TNF) therapy. METHODS: A systematic literature review was undertaken to identify studies of biologics approved for UC. Network meta-analysis was conducted for endpoints at induction and maintenance. RESULTS: Seven studies were included in the meta-analysis of induction treatment for anti-TNF therapy-naïve patients. All biologics were more effective than placebo in inducing clinical response, clinical remission, and mucosal healing. Infliximab demonstrated a statistically significant improvement over adalimumab in clinical response (odds ratio [OR] [95% credible interval (CrI)]: 2.19 [1.35-3.55]), clinical remission (OR [95% CrI]: 2.81 [1.49-5.49]), and mucosal healing (OR [95% CrI]: 2.23 [1.21-4.14]); there were no other significant differences between biologics for induction efficacy. Five studies were included in the meta-analysis of maintenance treatment, two studies rerandomised responder patients at end of induction, and three followed the same patients 'straight through'. To account for design differences, the number of responders at end of induction was assumed to be equivalent to the number rerandomised. Vedolizumab showed significantly different durable clinical response from comparators (OR [95% CrI] infliximab 3.18 [1.14-9.20], golimumab 2.33 [1.04-5.41], and adalimumab 3.96 [1.67-9.84]). In anti-TNF therapy-experienced patients, only vedolizumab and adalimumab could be compared. At induction, no significant differences in efficacy were seen. During maintenance, vedolizumab showed significantly improved rates of mucosal healing versus adalimumab (OR [95% CrI]: 6.72 [1.36-41.0]). CONCLUSIONS: This study expands the understanding of comparative efficacies of biologic treatments for UC, encompassing outcomes and populations not previously studied. All biologic treatments were effective for UC during induction. Vedolizumab demonstrated possible clinical benefits in the maintenance setting versus all comparators, irrespective of prior anti-TNF exposure and after adjusting for differences in study design.

Breast-specific gamma imaging in the detection of atypical ductal hyperplasia and lobular neoplasia.

RATIONALE AND OBJECTIVES: Atypical lesions such as atypical ductal hyperplasia (ADH) and lobular neoplasia are nonmalignant lesions that are associated with significant increased risk of developing breast cancer. Atypical lesions have been reported to present with focal increased radiotracer uptake on breast-specific gamma imaging (BSGI) examination, a novel physiologic tool for the detection of breast cancer. To date the sensitivity of BSGI in the detection of atypical lesions has not been reported. The purpose of this study is to determine the sensitivity of BSGI in detecting ADH and lobular neoplasia. MATERIALS AND METHODS: A total of 1316 patients who received a BSGI exam between January 2006 and July 2009 were retrospectively reviewed. All patients who underwent minimally invasive biopsy and subsequent surgical excision where the highest pathology was solely ADH or lobular neoplasia (reported as ALH, lobular carcinoma in situ or lobular neoplasia), according to the pathology database were included (n = 15). The sensitivity was determined as the percentage of positive BSGI exams out of all patients diagnosed with ADH or lobular neoplasia who received a BSGI. RESULTS: Patient ages ranged from 39 to 67 (mean, 52). Eight of 15 patients had ADH, 6/15 lobular neoplasia, and 1/15 ADH and lobular neoplasia in one lesion. Fifteen of the 15 (100%) patients with surgically confirmed ADH or lobular neoplasia had a positive BSGI, with focally increased radiotracer uptake at the site of the verified high-risk lesion. CONCLUSION: BSGI has a high sensitivity for the detection of atypical, high-risk breast lesions. A diagnosis of an atypical lesion is concordant with focal increased radiotracer uptake with BSGI and can identify women at increased risk for breast cancer.