Predicting outcomes in patients with advanced non-small cell lung cancer enrolled in early phase immunotherapy trials

Objectives: Immunotherapy (IO) has altered the non-small cell lung cancer (NSCLC) therapeutic landscape. However, the majority of patients do not respond to immune-checkpoint blockade, and subsequently either receive further chemotherapy or are referred for clinical trials. Here we examined the outcomes and predictors of response to IO in early phase clinical trials. Materials and methods: We analyzed the records of 74 patients with metastatic NSCLC that were enrolled on phase 1 trials within MD Anderson Cancer Center from 1/2010 to 7/2017. Results: The median age was 68, with a median follow-up of 12.3 months. The median lines of prior therapy was three. There were 53 patients who did not receive any IO as a prior line of treatment with a mOS of 8.2 months and mPFS of 3.4 months. There were 21 patients who progressed on a prior IO agent and subsequently went on an 10 study with a mOS of 10.5 months and mPFS of 4.3 months, which was similar to patients who did not receive 10 OS HR 0.81 (P = .51) and PFS HR 0.85 (P = .59). Royal Marsden Hospital (RMH) prognostic score > 1 was predictive of decreased OS HR 3.59 (P = .014) although PFS was not statistically different. MDACC prognostic score was predictive of both OS HR 3.39 (P = .0002) and PFS HR 1.9 (P = .030). ANC/ALC ratio (NLR) of > 6 was predictive of decreased survival mOS 3.2 months compared to NLR < 6 mOS 11 months; HR 3.0 (P = .0023). Conclusions: In our heavily pretreated patient population with NSCLC, early phase clinical trials with 10 demonstrated similar outcomes to those seen in larger clinical studies that also used immune checkpoint inhibitors. The addition of NLR to RMH and MDACC prognostic scores can identify patients with poor overall outcomes treated with early phase IO studies.