A15: The Identification of Clinically Relevant Primary Endpoints for Research for in Transit Melanoma Metastases

Aim: to assess the utility of surrogate markers of clinical response and their correlation to survival endpoints to generate clinically meaningful endpoints for ITMs research.




Methods: Cohort study (2005-20) from a supra-regional ITMs service providing isolated limb infusion and specialist locoregional treatments. Endpoints assessed included progression-free survival (PFS), time to progression (TTP), time to treatment failure (TTF), duration of response (DoR), overall response rate (ORR) and time to next treatment strategy (TTNTS: from locoregional to systemic), according to FDA definitions. The reference endpoints included DSS and distant metastasis-free survival (DMFS).


Results: 142 adults with ITMs were assessed. 19% had distant metastases at time of ITMs diagnosis and 68.7% mapped to AJCC stage IIIC. Median number of treatments was 4 [IQR:3-6]. The proportions of patients given local, regional and systemic treatments were 77%, 64% and 64%, respectively. Median PFS, TTP and TTF were 5, 5 and 4 months, and event rates were 97%, 92% and 94% respectively. The ORR for regional therapies was 80%. Regional ORR was not associated with improved DSS or DMFS. The median DoR for local, regional and systemic therapies were 4, 5 and 4 months respectively.  Median TTNTS survival was 21 (IQR:14-31) months and the event rate was 81%. On multivariate analysis, regional lymph node involvement was the only variable associated with worse TTNTS (HR=2.45 [1.46-4.10]; p< 0.001). TTNTS events were significantly associated with DMFS (HR=1.86 [1.2-2.87]; p< 0.001).


Conclusions: Our study identified TTNTS and DMFS as the most clinically relevant endpoints for ITMs, reflecting the chronic relapsing nature of the condition and allowing for cross-over of different treatment modalities without confounding analysis.