28P - Circulating biomarkers in non-small cell lung cancer patients treated with immune checkpoint inhibitors

Background

Patients with advanced Non-Small Cell Lung Cancer (aNSCLC), non-oncogene addicted, usually benefit from treatment with immune checkpoint inhibitors (ICIs), alone or in combination with cytotoxic agents (CT). However, only a portion of patients achieve durable clinical benefit from these drugs and serious adverse events, lead to treatment discontinuation in a fraction of patients. There is a clinical need to identify predictive biomarkers able to perform a patient selection and stratification.

Methods

A case series of 60 patients with aNSCLC treated with ICIs or CT+ICIs as a first line setting was considered. Tumor tissue at diagnosis and peripheral blood samples were collected at baseline for all patients and at progression disease (PD) for 9 patients. Plasma circulating tumor DNA (ctDNA) was sequenced by the TruSight™ Oncology 500 target panel in a NovaSeq 6000 platform with DRAGEN pipeline (Illumina). The neutrophil/lymphocyte ratio (NLR) was evaluated at baseline, first clinical evaluation and PD.

Results

Median age was 61 years (range 33-81), and 90% of patients were former or current smokers; 44 patients (73.3%) received CT+ICI, while 16 patients (26.6%)received only ICI. Landmark analysis was performed in 45 patients; when comparing molecular profile in ctDNA at baseline and PD, we found that 18 mutations were present only in ctDNA at baseline, 32 were found at both timepoints and 41 new mutations were identified in ctDNA at PD, involving several genes (i.e. mALK, MAPK, NRAS, PI3KCA, TP53, SMARCA4). Median TMB at baseline was 11.7 mut/mB, whereas median TMB at PD was 10.8 mut/mB. All patients were microsatellite stable (MSI score at baseline 2.8, MSI at PD 2.2). In 9 patients with available ctDNA at PD, ctDNA levels were higher at PD with respect to baseline (P=0.02). NLR was significantly higher at PD with respect to baseline in all the case series, especially in patients receiving ICIs (p<0.0001), suggesting changes in circulating white blood cells during treatment and at PD.

Conclusions

Patients with aNSCLC treated with an ICI-based treatment show an increase of somatic mutation rate and of NLR values at the time of PD. Statistical analysis in relation to progression free survival is ongoing.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.