1050P Does immunotherapy impact the outcomes of future anti-tumour therapies?

Abstract

Immune checkpoint inhibitors (ICI) have become a standard of care in oncology. However, little is known about their influence on the outcomes of subsequent treatment lines. We investigated the impact of prior exposure to ICI on the safety and efficacy of early-phase trial therapies. Patients (pts) from phase I/II trials, treated for melanoma, lung, head and neck, urothelial bladder, and renal cell cancer were included. Group A pts were immuno-naïve whereas group B pts had received at least one prior line of ICI-based therapy. Phase I/II trials included treatments based on ICI (IO) and non-immunologic therapies (NON-IO). The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and the advent of immune-related adverse events (irAE). We further assessed the prognostic value of the Royal Marsden Hospital (RMH) Score, Neutrophil/lymphocyte ratio (NLR) and Gustave Roussy Immune (GRIm) score. A total of 322 pts were included from 32 trials: 184 in group A and 138 in group B. The median number of prior lines was 1 [1-2] in group A and 3 [2-4] in group B. Administered therapies were classified as IO in 214 pts (132 in group A, 82 in group B) and NON-IO in 108 pts (52 in group A, 56 in group B). Pts from group B had a significantly shorter PFS (median [95%CI]: 82 days [61 – 91] vs. 156 days [117 – 193], HR: 1.75 [1.35 – 2.26], p<0.0001) and OS (338 [281 – 391] vs. 558 [397 – 806] days, HR: 1.78 [1.41 – 2.56], p <0.0001) than group A. PFS benefit in group B was confirmed in multivariate analysis (HR: 1.42 [1.06 – 1.91], p=0.02). Among pts treated with NON-IO, PFS was similar between groups A and B (p = 0.17). In pts treated with IO, PFS was shorter in group B than in group A, but similar to that of NON-IO therapies (p=0.95). Rate of IrAE was 14.6% in group B, 36.4% in group A (OR: 0.30 [0.15 – 0.60], p = 0.0005). The RMH score, NLR (median cut-off) and GRIm score significantly correlated with PFS in group A (p = 0.014, 0.004, and 0.0002, respectively) but not in group B (p = 0.18, 0.17, 0.17). In this study, pre-exposure to ICI was associated with reduced efficacy of early-phase trial immune therapies although comparable to non-immunologic therapies benefit in our series of patients. Additionally, pre-exposed patients were less likely to develop irAE.