2021P - Cell-free (cf) DNA as predictive biomarker (B) of treatment outcome in extensive small cell lung cancer (eSCLC) patients (pts) receiving atezolizumab, carboplatin and etoposide (ACE): CATS/ML43257 study

Background

First-line systemic therapy with ACE is a new standard of care for eSCLC. Circulating biomarkers may identify those pts experiencing a better treatment outcome.

Methods

The CATS study is a single center translational prospective study on eSCLC pts receiving ACE investigating the predictive role of circulating B. Plasma samples have been collected at 4 timepoints (T0 baseline; T1 after 1 cycle; T2 after 2 cycles; T3 disease progression). cfDNA has been analyzed by the Avenio ctDNA expanded kit.

Results

At data cut-off (1^st April 2023), 20 pts have been included. Preliminary results have been obtained from the first 11 pts (T0 n=11; T1 n=11; T2 n=10; T3 n= 6). After a median (m) follow-up (FUP) of 5.5 months (mo), response rate (RR) was 58.3% (95% Confidence Interval, CI 30.4-86.2), m progression-free survival (PFS) 4.8 (95%CI, 3.9-4.8) and m overall survival (OS) 11.2 mo (95%CI, 3.5-18.9). Median cfDNA was 52.3, 27.1 and 22.5 ng/mL, at T0, T1 and T2, respectively. A trend toward cfDNA level reduction between T0 and T1 (m 52.3 ng/mL; InterQuartile Ratio, IQR 12.8-122.7 vs 27.1, IQR 16.6-42.6, p=0.054) and a significant reduction between T0 and T2 (52.3, IQR 12.8-122.7 vs 22.5, IQR 11.1-38.0, p<0.05) were observed. Chromosomic profile (CP) was altered in 10 (90.9%), 4 (36.4%) and 4 cases (40%) at T0, T1 and T2, respectively. Tumor related mutations (TRM) were identified in all pts at T0 [TP53 in 11 (100%), RB1 in 5 (45.5%)] and at T1 [TP53 in 9 (81.8%), RB1 in 3 (27.3%)]; in 90% of pts at T2 [TP53 in 7 (70%), RB1 in 3 (30%)]. Median variant allele fraction (VAF) at T0, T1 and T2 was 38.3%, 1.2%, 0.2% and 30.7%, 33.1%, 20.1% for TP53 and RB1, respectively. In 8 (72.7%) pts, a VAF clearance was registered between T0 and T1 (p<0.001). Longer PFS was associated with low levels of cfDNA at T0 (p=0.04) and T2 (p=0.04). No correlation between the relative change of cfDNA at different timepoints and treatment outcome were observed at this preliminary analysis.

Conclusions

We suggest cfDNA, CP and TRM as putative circulating predictive biomarkers to be monitored in eSCLC pts receiving ACE. These data will be confirmed in a wider validation set of pts with a longer FUP.

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.