Validation of a clinical blood-based decision aid to guide immunotherapy treatment in patients with non-small cell lung cancer.

BACKGROUND The widespread introduction of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) has led to durable responses but still many patients fail and are treated beyond progression. OBJECTIVE This study investigated whether readily available blood-based tumor biomarkers allow accurate detection of early non-responsiveness, allowing a timely switch of therapy and cost reduction. METHODS In a prospective, observational study in patients with NSCLC treated with nivolumab or pembrolizumab, five serum tumor markers were measured at baseline and every other week. Six months disease control as determined by RECIST was used as a measure of clinical response. Patients with a disease control  95%, in order to allow its safe use for treatment decisions. RESULTS A total of 376 patients (training cohort: 180, validation cohort: 196) were included in our analysis. Results for the specificity of the single marker tests in the validation set were CEA: 98·3% (95% CI: 90·9-100%), NSE: 96·5% (95% CI: 87·9-99·6%), SCC: 96·5% (95% CI: 88·1-99·6%), Cyfra21·1 : 91.8% (95% CI: 81·9-97·3%), and CA125 : 86·0% (95% CI: 74·2-93·7%). A test based on the combination of Cyfra21.1, CEA and NSE accurately predicted non-response in 32.3% (95% CI 22.6-43.1%) of patients 6 weeks after start of immunotherapy. Survival analysis showed a significant difference between predicted responders (Median PFS: 237 days (95% CI 184-289 days)) and non-responders (Median PFS: 58 days (95% CI 46-70 days)) (p <  0.001). CONCLUSIONS Serum tumor marker based tests can be used for accurate detection of non-response in NSCLC, thereby allowing early and safe discontinuation of immunotherapy in a significant subset of patients.