Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma.

BACKGROUND: First-line chemotherapy for advanced esophageal squamous-cell carcinoma results in poor outcomes. The monoclonal antibody nivolumab has shown an overall survival benefit over chemotherapy in previously treated patients with advanced esophageal squamous-cell carcinoma. METHODS: In this open-label, phase 3 trial, we randomly assigned adults with previously untreated, unresectable advanced, recurrent, or metastatic esophageal squamous-cell carcinoma in a 1:1:1 ratio to receive nivolumab plus chemotherapy, nivolumab plus the monoclonal antibody ipilimumab, or chemotherapy. The primary end points were overall survival and progression-free survival, as determined by blinded independent central review. Hierarchical testing was performed first in patients with tumor-cell programmed death ligand 1 (PD-L1) expression of 1% or greater and then in the overall population (all randomly assigned patients). RESULTS: A total of 970 patients underwent randomization. At a 13-month minimum follow-up, overall survival was significantly longer with nivolumab plus chemotherapy than with chemotherapy alone, both among patients with tumor-cell PD-L1 expression of 1% or greater (median, 15.4 vs. 9.1 months; hazard ratio, 0.54; 99.5% confidence interval [CI], 0.37 to 0.80; P<0.001) and in the overall population (median, 13.2 vs. 10.7 months; hazard ratio, 0.74; 99.1% CI, 0.58 to 0.96; P = 0.002). Overall survival was also significantly longer with nivolumab plus ipilimumab than with chemotherapy among patients with tumor-cell PD-L1 expression of 1% or greater (median, 13.7 vs. 9.1 months; hazard ratio, 0.64; 98.6% CI, 0.46 to 0.90; P = 0.001) and in the overall population (median, 12.7 vs. 10.7 months; hazard ratio, 0.78; 98.2% CI, 0.62 to 0.98; P = 0.01). Among patients with tumor-cell PD-L1 expression of 1% or greater, a significant progression-free survival benefit was also seen with nivolumab plus chemotherapy over chemotherapy alone (hazard ratio for disease progression or death, 0.65; 98.5% CI, 0.46 to 0.92; P = 0.002) but not with nivolumab plus ipilimumab as compared with chemotherapy. The incidence of treatment-related adverse events of grade 3 or 4 was 47% with nivolumab plus chemotherapy, 32% with nivolumab plus ipilimumab, and 36% with chemotherapy alone. CONCLUSIONS: Both first-line treatment with nivolumab plus chemotherapy and first-line treatment with nivolumab plus ipilimumab resulted in significantly longer overall survival than chemotherapy alone in patients with advanced esophageal squamous-cell carcinoma, with no new safety signals identified. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 648 ClinicalTrials.gov number, NCT03143153.).

Real-world outcomes with second-line therapy in advanced esophageal squamous cell carcinoma using SEER-Medicare data.

Aim: To characterize real-world patterns of second-line treatment and outcomes in older patients with advanced/metastatic esophageal squamous cell carcinoma (ESCC). Patients and methods: Patients aged ≥66 years diagnosed with advanced/metastatic ESCC between 2010 and 2015 and followed through 2016 were included in this retrospective analysis using SEER-Medicare data. Results: Of 756 patients with advanced/metastatic ESCC, 104 (14%) received second-line therapy; median duration of treatment was 1.5 months. Median overall survival was 5.7 months for all patients receiving second-line treatment, and 4.5, 5.6 and 8.5 months, respectively, for patients receiving taxane monotherapy, taxane combination therapy and nontaxane therapy. Conclusion: A small proportion of patients with advanced/metastatic ESCC received second-line therapy, which was associated with short duration of treatment and poor overall survival.

This study assessed how US physicians have been treating a common type of esophageal cancer, known as squamous cell carcinoma, which has spread from the esophagus to other parts of the body (advanced/metastatic cancer). We looked at information from US cancer registry data on 756 people who were 66 years and older and diagnosed between 2010 and 2015. Only 14% of people received a second kind of chemotherapy after their first chemotherapy was stopped. People received their second chemotherapy for a short period (approximately 6 weeks) and lived for approximately 6 months on average from start of treatment. This research highlights that more effective treatments are needed for older people with advanced/metastatic esophageal squamous cell carcinoma.

Healthcare utilization and total costs of care among patients with advanced metastatic gastric and esophageal cancer.

Aim: Study first-line (1L) treatment patterns and economic outcomes among patients with advanced metastatic gastric cancer (GC) and esophageal cancer (EC). Materials & methods: Newly diagnosed patients with systemic GC and EC treatments were identified between 1 January 2011 and 31 July 2017; costs were presented as per patient per month (PPPM) basis. Results: Study included 392 GC and 436 EC patients. Most frequently used 1L regimens were: 5-fluorouracil (5-FU) + oxaliplatin (22.5%) and epirubicin + cisplatin + 5-FU (ECF)/ECF modifications (21.9%) in patients with GC; and carboplatin + paclitaxel (29.6%) and 5-FU + oxaliplatin (11.5%) in EC patients. Mean all-cause costs were US$16,242 PPPM for GC, and $18,384 PPPM for EC during 1L treatment. Conclusion: GC and EC were resource intensive and costly. High costs and short treatment durations underscored a gap in care in 1L treatment.

A global perspective in second-line treatment patterns for patients with advanced esophageal squamous cell carcinoma.

BACKGROUND: Esophageal cancer is a highly prevalent cancer associated with low survival, especially among those with advanced disease. Second-line (2L) treatment patterns and related clinical outcomes of patients with advanced esophageal squamous cell carcinoma (advESCC) treated in routine clinical care were examined globally and regionally. METHODS: A retrospective, noninterventional study collected physician-provided chart data of patients aged ≥20 years receiving either 2L active systemic therapy or BSC following first-line active therapy for advESCC from 11 countries in Asian and Western regions (September-October 2018). Bivariate analyses examined treatment and outcomes by region. RESULTS: AdvESCC patients (Asia = 192; West = 195) were examined, of which 58.1% (Asia n = 101; West n = 124) received active systemic therapy. While regional differences in tumor classification and staging at diagnosis were observed with less advanced tumors in Asia, no regional differences for these characteristics at 2L initiation were reported. Both taxane- and nontaxane-based therapies were used as 2L therapy among Asian and Western patients, although more western than Asian patients received immuno- or targeted therapies (17.0% vs. 3.0%; p = 0.001). Alopecia (10.7%), neutropenia (9.3%), and fatigue (9.3%) were the most-commonly reported adverse events (AEs) in both regions. Significantly higher 2L AE-related emergency room visits (Asia = 22.5% vs. West = 8.0%; p < 0.001) and hospitalizations (Asia = 25.9 ± 31.2 vs. West = 4.7 ± 7.0, p < 0.001) were observed in Asian than in Western patients. No regional differences were reported for response to 2L treatment or the percent of patients who received third-line treatment/died. CONCLUSIONS: While regional variations were observed throughout the course of a patient's advESCC journey, disease response and treatment outcomes were similar.

First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study.

PURPOSE: Nivolumab received US Food and Drug Administration approval as a single agent or in combination with ipilimumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan based on CheckMate 142. Presented are results of nivolumab plus low-dose ipilimumab in the first-line therapy cohort from the phase II CheckMate 142 study. PATIENTS AND METHODS: Patients with no prior treatment in the metastatic setting for MSI-H/dMMR CRC were treated with nivolumab every 2 weeks plus low-dose ipilimumab every 6 weeks until disease progression. The primary end point was objective response rate (investigator assessment; RECIST v1.1). RESULTS: Median age of treated patients was 66 years (N = 45). Median follow-up was 29.0 months. Objective response rate and disease control rate were 69% (95% CI, 53 to 82) and 84% (95% CI, 70.5 to 93.5), respectively, with 13% complete response rate. Median duration of response was not reached; 74% of responders had ongoing responses at data cutoff. Median progression-free survival and median overall survival were not reached with minimum follow-up of 24.2 months (24-month rates, 74% and 79%, respectively). Clinical benefit was observed regardless of baseline demographic and tumor characteristics, including BRAF or KRAS mutation status. In a post hoc analysis, of 14 patients who discontinued treatment and did not receive subsequent therapy, 10 remained progression-free. Patient-reported outcomes were stable over the treatment period. Grade 3-4 treatment-related adverse events occurred in 22% of patients; 13% discontinued because of any-grade treatment-related adverse events. CONCLUSION: Nivolumab plus low-dose ipilimumab demonstrated robust and durable clinical benefit and was well tolerated as a first-line treatment for MSI-H/dMMR mCRC. Based on these promising data, randomized studies are warranted.

Interpreting Premenstrual Symptoms Impact Survey scores using outcomes in health-related quality of life and sexual drive impact.

OBJECTIVE: To link the Premenstrual Symptoms Impact Survey (PMSIS) scores to health-related quality of life (HRQOL) and sexual drive impact associated with premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). STUDY DESIGN: Secondary data analysis was performed using the online survey study for PMSIS development. Women were sorted into 10 mutually exclusive score levels (N = 949). Their responses to the SF-12v2 Health Survey and the sexual drive question were dichotomized to indicate the presence of limitations/impairment. Chi-square analysis was conducted to compare the differences in percentages of women with limitations across 3 representative PMSIS score levels containing (1) women with no indication of PMS, (2) women at risk for PMS but not PMDD, and (3) women at risk for PMDD. RESULTS: The higher the PMSIS score level (more severe impact), the greater the percentage of women reported functional limitations. Women either at risk for PMS or PMDD were significantly more likely to report limitations than women with no indication of PMS in all HRQOL areas except for 2 Physical Functioning items and 1 Mental Health item and the General Health item. Significantly more women with PMS (67.5%) and with PMDD (73.3%) reported sexual drive impact than in women with no PMS (45.7%). CONCLUSION: The associations between PMSIS score levels and the premenstrual symptoms' impact on HRQOL and sexual functioning assist the interpretation of PMSIS scores and use of the tool in reproductive-age women.

The economic and safety impact of glass versus polymer containers in a radiology department.

Injuries and the resultant costs of injuries in today's healthcare environment are driving the need for healthcare to adopt measures to improve workplace safety for employees and increase safety for patients. Many imaging departments and facilities have implemented or are implementing safer engineering controls in an attempt to improve workplace safety. Newer options in contrast media packaging can provide alternative options engineered to improve workplace safety, avoiding risks with hidden physical and financial costs.

Cost-effectiveness analysis of treatments for premenstrual dysphoric disorder.

BACKGROUND: Premenstrual syndrome (PMS) is reported to affect between 13% and 31% of women. Between 3% and 8% of women are reported to meet criteria for the more severe form of PMS, premenstrual dysphoric disorder (PMDD). Although PMDD has received increased attention in recent years, the cost effectiveness of treatments for PMDD remains unknown. OBJECTIVE: To evaluate the cost effectiveness of the four medications with a US FDA-approved indication for PMDD: fluoxetine, sertraline, paroxetine and drospirenone plus ethinyl estradiol (DRSP/EE). METHODS: A decision-analytic model was used to evaluate both direct costs (medication and physician visits) and clinical outcomes (treatment success, failure and discontinuation). Medication costs were based on average wholesale prices of branded products; physician visit costs were obtained from a claims database study of PMDD patients and the Agency for Healthcare Research and Quality. Clinical outcome probabilities were derived from published clinical trials in PMDD. The incremental cost-effectiveness ratio (ICER) was calculated using the difference in costs and percentage of successfully treated patients at 6 months. Deterministic and probabilistic sensitivity analyses were used to assess the impact of uncertainty in parameter estimates. Threshold values where a change in the cost-effective strategy occurred were identified using a net benefit framework. RESULTS: Starting therapy with DRSP/EE dominated both sertraline and paroxetine, but not fluoxetine. The estimated ICER of initiating treatment with fluoxetine relative to DRSP/EE was $US4385 per treatment success (year 2007 values). Cost-effectiveness acceptability curves revealed that for ceiling ratios>or=$US3450 per treatment success, fluoxetine had the highest probability (>or=0.37) of being the most cost-effective treatment, relative to the other options. The cost-effectiveness acceptability frontier further indicated that DRSP/EE remained the option with the highest expected net monetary benefit for ceiling values

Burden of illness of hypertension among women using menopausal hormone therapy: a US perspective.

OBJECTIVE: To estimate the burden of illness (BOI) of hypertension in a cohort of women receiving menopausal hormone therapy (HT). METHODS: Patients with at least one prescription for menopausal HT were selected from the PharMetrics database during the period July 1, 2003, to June 30, 2005. Hormone therapy patients were divided into those with and without hypertension. The nonhypertensive cohort was propensity score-matched to the hypertensive cohort, controlling for patient demographics, overall comorbidities, and type of HT use. The BOI of hypertension in the menopausal HT cohort was defined as the difference in average annual total healthcare expenditures per person between the cohorts. RESULTS: The prevalence of menopausal HT use was 9.75% among potentially eligible patients in this commercially insured sample. Hypertension was the most common comorbidity in the menopausal HT cohort, with a prevalence of 34%. Hormone therapy patients with hypertension (n = 106,729) had significantly higher average annual healthcare expenditures compared to matched HT patients without hypertension ($8908 vs. $5960 per person per year; difference of $2948; p < 0.001). CONCLUSIONS: Hypertension is the most common comorbidity among menopausal HT users in the United States. The annual BOI of hypertension is both substantial and significant when compared to matched patients without hypertension, averaging $2948 per patient per year.

Cost effectiveness of contraceptives in the United States.

BACKGROUND: The study was conducted to estimate the relative cost effectiveness of contraceptives in the United States from a payer's perspective. METHODS: A Markov model was constructed to simulate costs for 16 contraceptive methods and no method over a 5-year period. Failure rates, adverse event rates and resource utilization were derived from the literature. Sensitivity analyses were performed on costs and failure rates. RESULTS: Any contraceptive method is superior to "no method". The three least expensive methods were the copper-T intrauterine device (IUD) (US$647), vasectomy (US$713) and levonorgestrel (LNG)-20 intrauterine system (IUS) (US$930). Results were sensitive to the cost of contraceptive methods, the cost of an unintended pregnancy and plan disenrollment rates. CONCLUSION: The copper-T IUD, vasectomy and the LNG-20 IUS are the most cost-effective contraceptive methods available in the United States. Differences in method costs, the cost of an unintended pregnancy and time horizon are influential factors that determine the overall value of a contraceptive method.

Advances in contraception: IUDs from a managed care perspective.

Contraceptive use in the United States is virtually universal among women of reproductive age. However, unplanned pregnancies continue to occur and can be largely attributed to the nonuse and misuse of contraception. Reducing unintended pregnancies constitutes a critical goal for managed care and the public. This can be achieved in part with intrauterine devices (IUDs), which are an effective method of contraception that require a one-time insertion and stay in place for 5-10 years. Therefore, compliance issues are largely mitigated, and actual use efficacy is the same as perfect use efficacy. The IUD is also reversible, unlike tubal ligation, and could potentially be the contraceptive of choice in today's environment. Unfortunately, safety concerns surrounding the use of older IUDs have precluded many women from recognizing the benefits of their use. Currently, the only approved IUDs in the United States are ParaGard, the copper IUD, and Mirena, the levonorgestrel-releasing intrauterine system (LNG-IUS). These devices offer superior safety profiles compared with those products that were withdrawn from the market in the 1970s. In addition to a favorable safety and tolerability profile, the LNG-IUS offers an advantage over copper IUDs, demonstrating improved efficacy in preventing intrauterine and ectopic pregnancies. Successful communication between patients and providers regarding the improved safety and efficacy of newer IUDs will ensure an appropriate place in therapy. Thus, greater numbers of women will recognize the IUD as a safe, cost-effective means to contraception, thereby reducing the economic and social burdens associated with unplanned pregnancies.