Transforming approaches to treating TRK fusion cancer: historical comparison of larotrectinib and histology-specific therapies.

OBJECTIVE: The results from basket trials utilized to gain regulatory approval of tumor-agnostic therapies can be difficult to interpret without the context of a comparator arm. We describe the role and efficacy of histology-based treatments to provide a historical comparison with larotrectinib. METHODS: A systematic literature review (SLR) was conducted on the clinical outcomes of current histology-based standard of care treatments used in non-small cell lung cancer, colorectal cancer, thyroid cancer, gliomas, soft tissue sarcoma, salivary gland cancer, and infantile fibrosarcoma (7 of the 21 tumor histologies in the larotrectinib trials). The review focused on advanced stage/metastatic disease to make a historical comparison with larotrectinib. RESULTS: Larotrectinib provides positive outcomes in both adult and pediatric patients with advanced or metastatic solid tumors known to harbor NTRK gene fusions across a wide range of tumor types. Although the numbers of patients per tumor type are limited, the results of this historical comparison demonstrated that larotrectinib is an efficacious treatment option when naïvely indirectly compared with historical treatments across all 7 reviewed tumor types, especially in comparison to later lines of therapy. CONCLUSIONS: Utilizing larotrectinib as a case example across these types of historical comparisons shows that larotrectinib provides positive efficacy outcomes in TRK fusion cancer across tumor histologies known to harbor NTRK gene fusions that may be preferable to historical treatments.

The burden of psoriatic arthritis: a literature review from a global health systems perspective.

OBJECTIVE: We sought to evaluate the clinical, economic, and humanistic burden of illness in patients with psoriatic arthritis (PsA). STUDY DESIGN: We performed a literature review. METHODS: Our literature search, conducted between 1998 and 2009, included published studies that (1) considered the direct and indirect costs of PsA; reported measures of clinical burden, including mortality, physical function, quality of life, and productivity; and (3) reported comorbid conditions in patients with PsA. RESULTS: We retrieved and reviewed a total of 49 studies. Compared with the general population, patients with PsA had lower health-related quality of life and an increased risk of co-morbid conditions, especially cardiovascular disease. In the U.S., the direct annual health care costs for PsA are estimated to be as high as $1.9 billion. Total indirect costs associated with PsA account for 52% to 72% of total costs. Both direct and indirect costs of PsA increase with worsening physical function and disease activity. CONCLUSION: PsA imposes a considerable economic and quality-of-life burden to patients and society. Clinical features of PsA, including comorbid conditions and disease activity, contribute to reduced physical and psychosocial health-related quality of life. The clinical burden of PsA contributes to direct medical costs attributable to the utilization of health care resources. As a result of the physical functioning limitations imposed by PsA, indirect costs such as disability and lost productivity are substantial drivers of the total costs of care.