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

Alissa J. Cooper, MD; Andrea Arfe, PhD; Biagio Ricciuti, MD; Andréanne Gagné, MD, PhD; Lynette M. Sholl, MD; Alessandro Di Federico, MD; Mark M. Awad, MD, PhD; Mihaela Aldea, MD, PhD; Maria Rosa Ghigna, MD; Miruna Grecea, MD; Phoebe Clark, MS; Jamie E. Chaft, MD; Mark G. Kris, MD; Gregory J. Riely, MD; Charles M. Rudin, MD, PhD; Ibiayi Dagogo-Jack, MD; Mari Mino-Kenudson, MD; Lingzhi Hong, MD, PhD; Neda Kalhor, MD; Natalie Vokes, MD; Anita Bowman, MS; Soo-Ryum Yang, MD; Natasha Rekhtman, MD, PhD; Adam J. Schoenfeld, MD

JTO Clinical and Research Reports (Jan 2025)

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

Alissa J. Cooper, MD,
Andrea Arfe, PhD,
Biagio Ricciuti, MD,
Andréanne Gagné, MD, PhD,
Lynette M. Sholl, MD,
Alessandro Di Federico, MD,
Mark M. Awad, MD, PhD,
Mihaela Aldea, MD, PhD,
Maria Rosa Ghigna, MD,
Miruna Grecea, MD,
Phoebe Clark, MS,
Jamie E. Chaft, MD,
Mark G. Kris, MD,
Gregory J. Riely, MD,
Charles M. Rudin, MD, PhD,
Ibiayi Dagogo-Jack, MD,
Mari Mino-Kenudson, MD,
Lingzhi Hong, MD, PhD,
Neda Kalhor, MD,
Natalie Vokes, MD,
Anita Bowman, MS,
Soo-Ryum Yang, MD,
Natasha Rekhtman, MD, PhD,
Adam J. Schoenfeld, MD

Affiliations

Alissa J. Cooper, MD: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Corresponding author. Address for correspondence: Alissa J. Cooper, MD, Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 545 E 73rd Street, New York, New York 10021.
Andrea Arfe, PhD: Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
Biagio Ricciuti, MD: Department of Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
Andréanne Gagné, MD, PhD: Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts
Lynette M. Sholl, MD: Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts
Alessandro Di Federico, MD: Department of Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
Mark M. Awad, MD, PhD: Department of Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
Mihaela Aldea, MD, PhD: Department of Medical Oncology, Gustave Roussy, Villejuif, France
Maria Rosa Ghigna, MD: Department of Pathology, Gustave Roussy, Villejuif, France
Miruna Grecea, MD: Department of Medical Oncology, Gustave Roussy, Villejuif, France
Phoebe Clark, MS: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
Jamie E. Chaft, MD: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
Mark G. Kris, MD: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
Gregory J. Riely, MD: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
Charles M. Rudin, MD, PhD: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
Ibiayi Dagogo-Jack, MD: Department of Medical Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts
Mari Mino-Kenudson, MD: Department of Pathology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts
Lingzhi Hong, MD, PhD: Department of Thoracic-Head & Neck Medical Oncology, MD Anderson Cancer Center, Houston, Texas
Neda Kalhor, MD: Department of Pathology, MD Anderson Cancer Center, Houston, Texas
Natalie Vokes, MD: Department of Thoracic-Head & Neck Medical Oncology, MD Anderson Cancer Center, Houston, Texas
Anita Bowman, MS: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
Soo-Ryum Yang, MD: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
Natasha Rekhtman, MD, PhD: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
Adam J. Schoenfeld, MD: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York

Journal volume & issue: Vol. 6, no. 1
p. 100759

Abstract

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Introduction: Thoracic 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. Methods: We collected clinical, pathologic, and demographic variables from five institutions for patients whose tumors met criteria for SMARCA4-UTs (undifferentiated phenotype and loss of SMARCA4 (BRG1) by immunohistochemistry). Results: We identified 92 patients with SMARCA4-UTs; 58 (63%) had stage IV disease at diagnosis and 16 (17%) developed recurrent or metastatic disease after initial diagnosis. Median overall survival from metastatic diagnosis was 7.3 (95% confidence interval [CI]: 4.6–12.8) months. Of patients with metastatic disease, 58 (78%) received first-line systemic treatment. Most often, patients received chemo and immunotherapy combination (41%), chemotherapy alone (33%), or immunotherapy alone (16%). Median progression-free survival from start of systemic therapy was 1.9 (95% CI: 1.4–14.5) months for chemo and 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 y); all received immunotherapy as part of first-line regimens. Nine (16%) of 55 tumor samples tested had programmed death-ligand 1 expression more than or equal to 50%, with 24 (44%) negative samples. Tumor mutational burden was available in 48 cases (52%), and median was 10.5 (range: 2–48) mutations per megabase. Conclusions: This multi-institution retrospective cohort analysis revealed a population of patients with short progression-free survival to standard therapies and poor overall survival. A few patients had 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.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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