Economic Burden Associated with Adverse Events in Patients with Metastatic Melanoma

Background: There are currently many approved agents for the treatment of metastatic melanoma (MM), the most aggressive form of skin cancer. Treatments may include systemic therapies such as ipilimumab, dacarbazine, temozolomide, high-dose interleukin 2, interferon α, dacarbazine- or temozolomide-based combination chemotherapy/biochemotherapy, paclitaxel, paclitaxel/cisplatin, and paclitaxel/carboplatin, as well as the targeted therapies vemurafenib, dabrafenib, and trametinib for patients with BRAF V600 mutation. However, all treatment options are associated with different adverse events (AEs) and, in some instances, considerable toxicity. The occurrence of such treatment-related AEs can lead to higher health care resource utilization and increasing treatment and patient management costs. An understanding of the economic burden of these AEs will therefore enable better management of health care expenditures, not just for existing therapies, but also for new and novel treatments in development.

Objective: To estimate the incremental health care costs of specific AEs among patients with MM treated with paclitaxel, vemurafenib, ipilimumab, dacarbazine, temozolomide, high-dose interleukin 2, or interferon α, along with AEs known to be associated with dabrafenib and trametinib.

Methods: This cohort study employed a retrospective administrative claims-based analysis of MarketScan commercial and Medicare supplemental databases from July 1, 2004, to April 30, 2012. Patients included those aged ≥ 18 years who had diagnosed melanoma (ICD-9-CM code 172.xx)with ≥ 1 diagnosis of metastasis and ≥ 1 claim for any of the 7 study treatments. Health care encounters for AEs of interest were based on ICD-9-CM diagnosis/procedure codes. Incremental cost per AE was determined by comparing the 30-day expenditures in patients with the event to patients without the event based on a shadow event date. Multivariate generalized linear models (GLMs) with a log-link function and gamma distribution were utilized to control for baseline differences between groups.

Results: A total of 2,621 patients with MM were included. Mean age was 56.0 years (SD ± 13.0); 64% were male; and 24% had a diagnosis of primary or secondary brain cancer at the time of MM diagnosis. GLM-based estimate of 30-day incremental costs by AE category were metabolic, $9,135 (95% CI = $6,404-$12,392); hematologic/lymphatic, $8,450 (95% CI = $6,528-$10,633); cardiovascular, $6,476 (95% CI = $4,667-$8,541); gastrointestinal, $6,338 (95% CI = $4,740-$8,122); skin/subcutaneous, -$900 (95% CI = -$1,899-$237); central nervous system/psychiatric, $5,903 (95% CI = $3,842-$8,313); and pain, $5,078 (95% CI = $3,392-$7,012).

Conclusions: Incremental costs associated with many MM treatment-related AEs are substantial. New approaches to prevent and/or better manage these events may reduce overall health care costs.