14P - SLFN11 detection in patients with small cell lung cancer treated with lurbinectedin: A retrospective translational analysis

Background

Schlafen (SLFN11) is an emerging prognostic and predictive biomarker in small cell lung cancer (SCLC); when downregulated, no replication arrest occurs in the presence of DNA damage. Lurbinectedin binds to GC-rich areas of gene promoters, blocks the RNA polymerase II, and induces DNA breaks and apoptosis. The SLFN11 predictive role to lurbinectedin has been shown in tumor cells and xenografts, but not explored in patients receiving lurbinectedin.

Methods

This retrospective translational study included SCLC patients (pts) treated with lurbinectedin in second or further lines. The primary aim was to evaluate the correlation of SLFN11 expression with median progression free survival (mPFS) to lurbinectedin. Secondarily, we investigated the correlation of SLFN11 expression with median overall survival (mOS) and mPFS to first line (1L) with platinum and etoposide (PE) ± atezolizumab and to second line (2L) therapy (topotecan or PE rechallenge). Baseline tumor tissue was analyzed by multiplex immunofluorescence to explore the correlation between SLFN11 levels and the immune infiltration in the tumor microenvironment. Pts were stratified based on the median percentage of SLFN11+ tumor cells (9%) in SLFN11 high (SLFN11-H) and low (SLFN11-L).

Results

Preliminary results on the first 15 pts are reported; ten (66.7%) received lurbinectedin as 2L, five (33.3%) as third line. A trend towards a longer mPFS to lurbinectedin was observed in SLFN11-H pts, as well as to other 2L treatments, although without statistical significance. A longer mPFS to 1L therapy (9.1 vs 5.2 months, p=0.004, HR 0.12, 95%CI 0.24-0.63) and mOS (31.2 vs 14.1 months, p=0.022, HR 0.21, 95%CI 0.53-0.89) were observed in SLFN11-H pts. SLFN11 levels were higher in the tumor than in the stroma (p=0.014) and were variably expressed in infiltrating immune cells; a higher density of CD163+ macrophages (p=0.020), and a lower density of intratumoral CD20+ B lymphocytes (p=0.027) were observed in SLFN11-H pts.

Conclusions

SLFN11 higher expression correlates with better outcomes to 1L therapy and suggests a predictive value to lurbinectedin in second or further lines. Validation analyses on a wider population are currently ongoing and will be presented at the conference.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Veneto Institute of Oncology.

Funding

Fondi Ricerca Corrente Oncologia 2 IOV; Fondi DOR DISCOG Università degli Studi di Padova.

Disclosure

L. Bonanno: Financial Interests, Institutional, Advisory Board: AstraZeneca, MSD, BMS, Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca, MSD, BMS, Roche, AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Lilly; Non-Financial Interests, Personal, Principal Investigator: Roche, AstraZeneca, Boehringer Ingelheim, MSD, BMS, Janssen, PharmaMar, Arcus Biosciences. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, GSK, AstraZeneca, Gilead, Exact Sciences; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Merck Serono, Exact Sciences, Eisai, Olema Oncology, AstraZeneca, Daiichi Sankyo, Pfizer; Financial Interests, Personal, Expert Testimony: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, GSK, Daiichi Sankyo, Nerviano, Pfizer; Non-Financial Interests, Personal, Member: ASCO. G. Pasello: Financial Interests, Personal, Invited Speaker: Amgen, Eli Lilly, Novartis, MSD, Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Janssen; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Other, unconditioned support: AstraZeneca, MSD; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, Roche, Novartis, Lilly, Janssen, PharmaMar. All other authors have declared no conflicts of interest.