2020P - Circulating micro RNAs (cmiRNAs) as treatment outcome predictors in extensive small cell lung cancer (eSCLC) patients (pts) receiving atezolizumab plus carboplatin and etoposide (ACE): CATS/ML43257 study

Background

ACE is the new standard first-line treatment for eSCLC. However, response to this treatment is highly heterogeneous and the identification of patients more likely to benefit from immunotherapy is in high demand. To this end, circulating biomarkers may prove to be useful, especially when tumor tissue samples are difficult to obtain and for tumors with high genetic heterogeneity. CATS is a prospective pilot study aiming at identifying predictive cmiRNAs in a cohort of eSCLC patients receiving ACE.

Methods

Next generation sequencing technology was employed to determine the cmiRNA profile in the plasma of eSCLC patients at different time points (T0 baseline; T1 after 1 cycle; T2 after 2 cycles; T3 disease progression). Library preparation was carried out using the QIAseq miRNA library kit (Qiagen, Hilden, Germany). All samples were single-end-sequenced on an Illumina NextSeq500 platform. The mean number of miRNA with more than 5 reads detected in the samples was 326. Cut-off values for definition of low versus high levels of miRNA were identified over and under the median value. Univariate (log rank test) analyses were performed to investigate the possible impact of cmiRNA levels on progression-free survival (PFS).

Results

Overall 20 patients have been enrolled in the study. Preliminary results have been obtained for 11 patients (T0 n=11; T1 n=11; T2 n=11; T3 n= 7), with a median follow-up of 5.5 months. Median PFS was 4.8 months. We observed no correlation between the baseline levels of cmiRNAs and tumor load and proliferation index. A panel of 4 cmiRNAs targeting transcription factors was identified as significantly correlated with PFS, both individually (p=0.001, p=0.002, p=0.006; p=0.008, respectively) and within a combined score (p=0.001). No significant predictive value of the relative change between timepoints of these cmiRNAs was observed.

Conclusions

Baseline levels of specific cmiRNAs may identify eSCLC pts with different PFS to first line ACE. Results from a wider cohort of patients with longer follow-up and the validation of the proposed miRNAs will presented at the conference.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

University of Padua.

Funding

Istituto Oncologico Veneto (project funding P8); Roche.

Disclosure

All authors have declared no conflicts of interest.