The concept of functional cure in advanced/metastatic melanoma treated with combined nivolumab and ipilimumab or nivolumab alone.

backgroundImmune-Checkpoint-Inhibitors (ICIs) have significantly improved the course of advanced/metastatic melanoma and the concept of ICIs curative potential began to appear. To use statistical approaches to determine whether advanced/metastatic melanoma patients treated with nivolumab alone or in combination with ipilimumab may be considered as functionally cured.

methodsIndividual patient data were reconstructed from published Kaplan-Meier curves of the anti-PD1 arms of the Checkmate-067. The assumption of functional cure was assessed using three approaches based on a flexible-parametric survival model. Once the hypothesis of functional cure was confirmed, the time to functional cure (TTFC) was determined using an intuitive approach based on flexible survival model.

resultsThe three complementary approaches were consistent and confirmed the functional cure assumption. The TTFC (the shortest time defined by fewer than 1% of patients progressing or dying) was estimated to be 61 (95%CI,50.7;79.4) and 63 m (95%CI,51.1;71.4) for nivolumab alone or in combination, respectively.

conclusionsWe showed that metastatic melanoma patients, treated with the combination or nivolumab alone who were alive and had not progressed by the five-year time-point, can be considered as functionally cured. The robust statistical approach proposed could be applied to other clinical settings when the plausibility of cure is to be validated.