FDA analysis of depth of response (DpR) and survival across 10 randomized controlled trials in patients with previously untreated unresectable or metastatic melanoma (UMM) by therapy type.

Abstract

9508 Background: Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 may not capture the full spectrum of benefit that patients with melanoma derive from targeted kinase inhibitors (TKI) or immunotherapies. We explored the relationship between DpR and overall survival (OS) in patients treated with TKI (BRAF, MEK inhibitors), immunotherapy (antibodies targeting PD-1 or CTLA-4), or chemotherapy (dacarbazine or paclitaxel). Methods: Ten randomized controlled trials of patients with previously untreated UMM were pooled and evaluated by type of therapy. DpR was grouped by maximal tumor shrinkage (G0 = no shrinkage or increase, G1 = ≤25%, G2 = 26-50%, G3 = 51-75%, G4 = 76- < 100%, and G5 = 100%). We performed an exploratory analysis evaluating the association between DpR and OS using hazard ratios (HR) generated from a Cox proportional hazards model where maximal tumor shrinkage category was included as a time varying covariate. Results: There were 3778 patients evaluable for tumor response. The table displays the HR for OS by DpR group and therapy type. Estimated OS at 24m in patients with deep response ( > 75%; G4+G5) treated with TKI and immunotherapy was 69% and 92%, respectively, although many patients were censored. Conclusions: For patients with previously untreated UMM a larger DpR correlates with a longer OS, regardless of therapy type. Deep response ( > 75%) is associated with a high rate of estimated OS at 24 months in patients treated with immunotherapy. Analysis of DpR provides additional granularity of response data and may provide a more nuanced prediction of clinical outcome. [Table: see text]