External control cohorts for the single-arm LIBRETTO-001 trial of selpercatinib in RET+ non-small-cell lung cancer.

BACKGROUND: Data for selpercatinib [a selective REarranged during Transfection (RET) inhibitor] from a single-arm trial (LIBRETTO-001, NCT03157128) in RET-fusion-positive advanced/metastatic non-small-cell lung cancer (NSCLC) were used in combination with external data sources to estimate comparative efficacy [objective response rate (ORR), progression-free survival, and overall survival (OS)] in first- and second-line treatment settings. METHODS: Patient-level data were obtained from a de-identified real-world database. Patients diagnosed with advanced/metastatic NSCLC with no prior exposure to a RET inhibitor and one or more prior line of therapy were eligible. Additionally, individual patient-level data (IPD) were obtained from the pemetrexed + platinum arm of KEYNOTE-189 (NCT03950674, first line) and the docetaxel arm of REVEL (NCT01168973, post-progression). Patients were matched using entropy balancing, doubly robust method, and propensity score approaches. For patients with unknown/negative RET status, adjustment was made using a model fitted to IPD from a real-world database. RESULTS: In first-line unadjusted analyses of the real-world control, ORR was 87.2% for LIBRETTO-001 versus 66.7% for those with RET-positive NSCLC (P = 0.06). After adjustment for unknown RET status and other patient characteristics, selpercatinib remained significantly superior versus the real-world control for all outcomes (all P < 0.001 except unadjusted RET-fusion-positive cohort). Similarly, outcomes were significantly improved versus clinical trial controls (all P < 0.05). CONCLUSIONS: Findings suggest improvement in outcomes associated with selpercatinib treatment versus the multiple external control cohorts, but should be interpreted with caution. Data were limited by the rarity of RET, lack of mature OS data, and uncertainty from assumptions to create control arms from external data.

Long-term cost and life-expectancy consequences of hypertension.

OBJECTIVE: To estimate hypertension's long-term cost and impact on life expectancy. DESIGN: A 19-year individual follow-up study. Subjects were categorized according to their baseline (1972) diastolic blood pressure (DBP) level into three groups: normotensive (DBP < 95 mmHg), mildly hypertensive (DBP 95-104 mmHg), and severely hypertensive (DBP > 104 mmHg). By using their social security identification numbers, we linked the subjects to a set of national registers covering hospital admissions, use of major drugs, absence due to sickness, disability pensions, and deaths. SUBJECTS: A random population sample of 10 284 men and women aged 25-59 years from the provinces of Kuopio and North Karelia in eastern Finland. MAIN OUTCOME MEASURES: The numbers of years of life and years of work lost, the cost of drugs and hospitalization, and the value of productivity lost due to disability and premature mortality. RESULTS: The difference in life expectancy between normotensive and severely hypertensive men was 2.7 years, of which 2.0 years was due to cardiovascular disease (CVD). Among women the corresponding differences were 2.0 and 1.5 years. Severely hypertensive men lost 2.6 years of work more than did normotensive men, of which 1.7 years was due to CVD. Among women the differences were 2.2 and 1.3 years. The mean undiscounted total costs (USA dollars at 1992 prices) were $132 500 among normotensive, $146 500 among mildly hypertensive, and $219 300 among severely hypertensive men, of which CVD accounted for 28, 39, and 43%, respectively. More than 90% of the total costs were indirect productivity losses. Among women the total costs were lower for all DBP categories, as were the shares of CVD-related costs. The proportional increase in costs on going from the lowest to the highest DBP category was, however, somewhat larger among women. CONCLUSIONS: On the population level, severe hypertension leads to considerable losses in terms of years of life lost, years of work lost, and costs. However, the overall impact of mild hypertension is much more limited.

Does prevention of cardiovascular diseases lead to decreased cost of illness? Twenty years of experience from Finland.

BACKGROUND: During the past 20 years the age-standardized cardiovascular disease mortality rate has declined in Finland by 50%. The aim of this study was to examine the social cost consequences of this decline. METHODS: The prevalence-based cost-of-illness analysis was applied to estimate both direct and indirect costs of cardiovascular disease in 5-year intervals from 1972 to 1992 (in 1992 prices). Summary data from the national registers covered all persons with cardiovascular disease who were treated, received sickness insurance benefits, or died from the disease. RESULTS: Direct health care costs increased, but the decline in indirect costs overcompensated that increase. The total cost among all persons age 35 and over, including the retired, was $2.7 billion in 1972 and $2.6 billion in 1992, which is a 4% decrease. In the age group of 35-64 years the total costs fell from $2.5 billion to $1.9 billion (25%). In terms of cost per capita the decline was 26 and 40% in the respective age groups. CONCLUSIONS: The costs of cardiovascular disease decreased since 1972. However, total costs declined clearly less than the cardiovascular disease mortality rate. This implies that considerable savings in total costs, especially in direct health care costs, may not be expected as a result of even very successful prevention programs.