Using real-world claims data, this study identified populations that had undergone surgery for malignant melanoma and subsequently received IFN therapy or non-IFN standard of care chemotherapy. According to the indications for IFN and non-IFN chemotherapies, these treatments describe adjuvant therapy for patients with Stage IIB to III malignant melanoma and with Stage IV metastatic melanoma, respectively.
For the population who received IFN therapy, the duration of total therapy (induction and maintenance combined) was on average 3–5 months. However, approximately 50% of patients discontinued therapy within or after induction, for reasons that cannot be obtained from an administrative claims database study like this. The median number of total doses for IFN therapy was 20, corresponding to the total number of doses for the induction phase according to the Intron A product label.7
This indicates that patients seem to complete the induction phase of therapy which requires infusion, and then discontinue, not moving onto the self-administered maintenance phase of therapy. Further study to investigate reasons for discontinuation may be warranted. In addition, 91% of patients were on IFN therapy for some period of time during a one-year period. There is no known published source regarding the duration of IFN therapy as observed in the pivotal clinical trials, but the median relapse-free survival for IFN observed was 1.72 years compared with 0.98 years for observation.14
To optimize treatment outcomes, it is important to adhere to recommended therapy regimens. A study by Agarwala et al indicated that 4 weeks of therapy with IFN, equivalent to the induction phase alone, did not show improvement in relapse-free survival (6.8 years compared with 7.3 years for observation) in patients with intermediate (81% of IFN-treated population) or high-risk (19% of IFN-treated population) melanoma.15
This is in contrast with the increase observed in the pivotal trial, noted earlier.14
However, there is no publicly available scientific source documenting the duration of IFN therapy from either of these trials. The study by Agarwala et al suggests that longer duration of IFN treatment may be important.15
Adherence to the recommended dosage and administration of IFN in the high-risk population should be an important part of patient education to maximize the benefits of therapy.
Possible factors contributing toward discontinuation of IFN therapy may be inconvenience of infusion administration and frequency of therapy during the induction phase, as well as toxicity related to therapy.16
Newer therapies are available for Stage III disease, such as a PEGylated version of IFN (Sylatron™) which, in contrast with non-PEGylated interferons, allows for less frequent dosing because of delayed renal clearance. In addition, dosing modification guidelines exist for PEGylated IFN which are intended to manage any associated toxicity and allow patients to stay on therapy for as long possible. The proposed course of treatment with PEGylated IFN for melanoma involves an induction phase of one dose per week subcutaneously for 8 weeks, followed by a maintenance phase of half that dose once per week subcutaneously for up to 5 years.17
This dosing form allows for self-administration, thereby eliminating costs associated with infusion, such as for IFN.
Two of the largest cost components of the annual direct cost of diagnosing and treating melanoma in the US are reported from a modeling study to be adjuvant IFN therapies (27%, $151 million) and terminal care (35%, $197 million).18
This was confirmed by a US economic model that found the most expensive elements of medical care among patients with melanoma to be adjuvant IFN therapy at about $76,000 per patient, and palliative care at $14,500 per patient.19
This is supported by another US study which showed that hospital services were the main contributor to the high cost of malignant melanoma on a per patient basis among subjects aged 65 years and older who had a malignant melanoma diagnosis of at least stage IIB or higher.9
Differences in methodology among studies preclude direct comparison of cost results.
For the current study, cost refers to the amount paid to providers associated with the health service; because these are reimbursement rates, actual costs could be lower than what is reported. Looking at the study results, average unit costs for surgery itself accounted for most of a patient’s total melanoma-related surgery costs at $1046 out of $2219. The average unit cost for IFN drug therapy only was $814, while average unit costs for other chemotherapy drugs ranged from $146 to $2678. However, these values should be taken in context with the patient populations they treat, IFN is used for patients with Stage IIB to III disease, which are a larger segment of the melanoma patient population compared with patients at Stage IV. In addition, patients at the earlier stages have a better chance for survival and continuing on treatment. Further, the number of single-agent or combination regimen chemotherapy cycles completed also contributes toward the cost. Therefore, comparisons cannot be made in this regard.
There were limitations in conducting this retrospective database study. The stage of disease could not be confirmed due to the absence of staging information in the database; it was assumed that receipt of IFN therapy following surgery defined patients with at least regional disease. Secondly, the proportion of patients that were part of a clinical trial was unknown and may influence claims generated if services were reimbursed by other sources, thus causing potential for underestimation of some costs. Also, inclusion of only fee-for-service patients may have introduced selection bias, though the majority of patients were enrolled in this plan type. Lastly, patient adherence could not be assessed due to lack of information on aspects such as disease management and how IFN was administered during the treatment phases.