Abstract
After more than two decades with interferon alfa-2a and 2b (IFN) as the only approved drugs in the adjuvant setting for melanoma, new treatment approaches like immune checkpoint inhibitors and BRAF-MEK inhibitors improve the progression free survival (PFS) and also the overall survival (OS).We compared physicians' preferences (“utilities”) for health states associated with IFN therapy to their patients' preferences. Utilities describe a preference for a specific health state on a scale of 0 (as bad as death) to 1.0 (perfect health).SettingWe assessed utilities for health states associated with adjuvant IFN using the standard gamble technique in 108 physicians and 130 melanoma patients. Four IFN toxicity scenarios and three outcome scenarios were given to the participants. Both groups were asked for the 5-year disease free survival (DFS) they would need to accept the described IFN-related side effects.ResultsIn both groups, utilities for melanoma relapse were significantly lower than for IFN side effects, showing that toxicity was more acceptable than relapse. Physicians indicated higher utilities for each scenario and needed lower 5-year DFS both in case of mild-to-moderate and severe side effects. Patients were willing to tolerate mild-to-moderate and severe toxicity for a 50% and 75% chance of 5-year DFS, while physicians only required a chance of 40% and 50%, respectively.ConclusionBoth physicians and patients rated melanoma recurrence much lower than even severe IFN side effects. In direct comparison, physicians rated cancer-related scenarios more positively and accepted IFN toxicity for an even lower treatment benefit.
Highlights
The high risk melanoma patient population is heterogeneous, with disease-free survival (DSF) rates of 78%, 59% and 40% for stage IIIA, IIIB and IIIC, respectively [1,2,3]
Setting: We assessed utilities for health states associated with adjuvant interferon alfa-2a and 2b (IFN) using the standard gamble technique in 108 physicians and 130 melanoma patients
In both groups, utilities for melanoma relapse were significantly lower than for IFN side effects, showing that toxicity was more acceptable than relapse
Summary
The high risk melanoma (nodal involvement AJCC stage III) patient population is heterogeneous, with DSF rates of 78%, 59% and 40% for stage IIIA, IIIB and IIIC, respectively [1,2,3]. Recently approved drug modalities like BRAF-MEK and immuncheckpoint inhibitors improved the prognosis of high risk-melanoma patients (DFS HR.47-.72) markedly [4, 5]. Adjuvant treatment has a specific toxicity profile, which is why physicians need to thoroughly discuss the individual risk-benefit ratio with eligible patients. This decision making process may be influenced by the physician’s personal convincement. Clinical trials showed a positive effect of both targeted therapy and immune checkpoint blockade in the adjuvant setting [4, 6, 7] With these new drug modalities, it is possible to improve DFS and for some OS. We already know from other tumor entities that patients and physicians rate benefit-risk ratios differently [8, 9]
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