P3.01-74 Clinical and Radiological Predictors of Efficacy to Nivolumab in NSCLC: A Multi-Institutional, Retrospective Cohort Study.

Abstract

Identification of sub-populations of patients with a greater likelihood of response to anti-programmed death-1 (PD1) inhibitors in non-small cell lung cancer (NSCLC) would enable treatment to be directed to those most likely to benefit, thereby increasing efficacy and cost effectiveness. The relationship, however, between clinical and radiological parameters with efficacy of single agent Nivolumab remains unclear in advanced NSCLC. A retrospective analysis was conducted for patients who received second-line Nivolumab following progression after platinum based chemotherapy for advanced NSCLC on a Compassionate Access Program across seven oncology institutions in Queensland, Australia. ECOG Performance status (PS), immune related adverse events (IrAEs), and baseline CT texture analysis (as a surrogate for tumour heterogeneity) was assessed. The endpoints were overall survival (OS), progression free survival (PFS) and objective response rate (ORR). An institutional ethical approval was obtained. Two hundred and fourteen patients were enrolled over two years, median age 67 (range 42 to 84 years). PS 0-1 (64 %); PS 2-3 (36%). The median OS was 8.9 months (95% CI, 6.6 to 11.67); 13.3 months in PS 0-1 patients and 4.9 months in PS 2-3 patients. At 1 year, the OS rate was 41%; 55% in patients with PS 0-1 and 19% in PS 2-3 patients. ORR was recorded in 23% of patients (50/214), an additional 27% (58/214) had stable disease. Toxicity data was available for 90% of patients (N=194). The presence of IrAEs of any grade occurred in 36% of patients and was associated with a longer median PFS of 5.9 months versus 2.3 months in patients with no immune toxicity (P value <0.01, 95% CI). In patients with IrAE the ORR was 32% versus 18%, 1 year OS 59% versus 29% in those without any immune mediated toxicity. CT texture analysis findings (N=47) consistent with increased tumour heterogeneity showed significantly longer PFS (median NR versus 1.5 months, Hazard Ratio: 2.05, p=0.018). We found Nivolumab had clinically significant long-term benefits in the treatment of locally advanced and metastatic NSCLC with 12 month survival rates in keeping with clinical trials in PS 0-1 patients. An ECOG PS 0/1, the development of IrAEs and increased tumour heterogeneity by CT texture analysis was associated with a significantly longer PFS and increased clinical benefit in this cohort. The combination of these clinical and radiological parameters may identify subgroups of patients benefitting from this therapy.