Brief Report: Clinical Characteristics and Outcomes of Patients with Thoracic SMARCA4-Deficient Undifferentiated Tumors

Abstract

IntroductionThoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UTs) are a recently-defined group of aggressive cancers in which the effectiveness of standard treatments for lung cancer is unknown. MethodsWe collected clinical, pathological, and demographic variables from 5 institutions for patients whose tumors met criteria for SMARCA4-UTs (undifferentiated morphology and loss of SMARCA4/BRG1 by immunohistochemistry). ResultsWe identified 92 patients with SMARCA4-UTs; 58 (63%) had stage IV disease at diagnosis, and 16 (17%) developed recurrent/metastatic disease after initial diagnosis. Median overall survival (OS) from metastatic diagnosis was 7.3 (95% CI: 4.6-12.8) months. Of patients with metastatic disease, 58 (78%) received first-line systemic treatment. Most commonly, patients received chemo/immunotherapy combination (41%), chemotherapy alone (33%), or immunotherapy alone (16%). Median progression-free survival (PFS) from start of systemic therapy was 1.9 (95%CI: 1.4-14.5) months for chemo/immunotherapy, 1.6 (95%CI: 1.1-5.8) months for chemotherapy, and 3.3 (95%CI: 1.2-undefined) months for immunotherapy alone. Five patients had durable responses (≥ 2 years); all received immunotherapy as part of first-line regimens. Nine (16%) of 55 tumor samples tested had PD-L1 expression ≥50%, with 24 (44%) negative samples. Tumor mutational burden was available in 48 cases (52%), median was 10.5 (range 2-48) mutations/megabase. ConclusionsThis multi-institution retrospective cohort analysis revealed a population of patients with short PFS to standard therapies and poor OS. A few patients demonstrated remarkable response to regimens including immunotherapy. Prospective clinical studies are urgently needed to identify better therapeutic approaches to treat this aggressive malignancy and this analysis may serve as a benchmark for future clinical trial design.