Abstract 179P
Background
SMARCA4/SMARCB1 are components of the SWI/SNF complex that have been implicated in the development and early dedifferentiation of several tumors, through the loss of its chromatin-remodeling activity. The prognostic value of SMARCA4 inactivation has been described in the setting of lung cancer although evidence of ICB-sensitivity is scarce.
Methods
We performed an observational retrospective study at Hospital Clinico Universitario San Carlos (Madrid) in 162 NSCLC patients undergoing NGS testing of their disease between July 2019 and December 2021. We analyzed clinical data, response to immunotherapy, tumor mutational burden (TMB) and accompanying genetic alterations.
Results
We identified 17/162 (10.5%) patients with SMARCA4/B1 alterations, with a median age of 62 years (range 40-82), a dominance of men (12 patients, 70%) and tobacco exposure (15 patients, 88%). The most common histology was adenocarcinoma (65%). Median TMB was 13.87 mut/Mb (range 1.26-60.52). Six patients (35%) had a tumoral PD-L1 expression ≥ 50%, 3 pts presented 1-49% and another 6 patients (35%) had a negative PD-L1 expression. SMARCA4 alterations consisted of point mutations in 13 patients (76.5%), followed by single cases of a frameshift mutation and a splicing modification. Only 2 patients presented point mutations in SMARCB1. In SMARCA4/B1-altered tumors, the most frequently altered gene was TP53, (14 patients, 82.4%) followed by RICTOR mutations and CDKN2A/B loss (7 and 6 patients, respectively). Pathological alterations in KRAS and EGFR were detected in 4 and 3 patients respectively. ICB was administered in 12 patients with SMARCA4/B1-altered tumors (1st line pembrolizumab in monotherapy or in combination in 83% for metastatic disease). Median PFS for all immunotherapy-treated patients was 360 days (95%CI 158-562).
Conclusions
In our cohort, patients with genetic alterations in SMARCA4/SMARCB1 genes presented high TMB and prolonged responses to immunotherapy. The incorporation of NGS in clinical care refines clinical profiling of patients and can potentially improve treatment selection.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
G. Fernandez: Financial Interests, Personal, Advisory Role: CancerAppy. A. Ocaña: Financial Interests, Institutional, Full or part-time Employment, No conflict of interest in relation to this data: Symphogen. All other authors have declared no conflicts of interest.