Therapeutic outcomes in non-small cell lung cancer with <i>BRAF</i> mutations: a single institution, retrospective cohort study.

Abstract

Background

Data describing therapeutic outcomes in patients with non-small cell lung cancers (NSCLC) with BRAF mutations remains limited.

Methods

We conducted a retrospective cohort study of 31 patients with metastatic NSCLC treated at Duke University Hospital who had been identified by next-generation sequencing methods to bear a BRAF mutation in their tumor in order to evaluate clinical response to immunotherapy and chemotherapy.

Results

Sixty-five percent of patients identified in this cohort were current or former smokers. Fourteen (45.2%) of patients had a BRAF V600E mutation and 17 (54.8%) had a non-V600E mutation. Median progression-free survival (PFS) in the 23 patients who received first-line chemotherapy was 6.4 months [95% confidence interval (CI), 2.3 to 13.0]. Overall survival (OS) in patients who received first-line chemotherapy showed a median survival of 18 months (95% CI, 7.4 to 28.6). OS comparing patients who had never received immunotherapy at any point was 18.4 months (95% CI, 4.1 to NE) compared to 19.0 months (95% CI, 9.9 to 28.6) in those who had received immunotherapy. We did not find a statistically significant difference in OS in patients with BRAF V600E, BRAF amplification, or non-V600E mutations. There was also no difference in OS in patients treated with targeted BRAF inhibitors compared to those who were not treated with targeted BRAF inhibitors.

Conclusions

We describe therapeutic outcomes for patients with metastatic NSCLC with BRAF mutations treated with either cytotoxic chemotherapy or immunotherapy. Although the sample size is small, the survival curves do not suggest improved clinical activity in this population when treated with immunotherapy.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.21037/tlcr.2019.04.03

Publication Info

Tan, Irena, Thomas E Stinchcombe, Neal E Ready, Jeffrey Crawford, Michael B Datto, Rebecca J Nagy, Richard B Lanman, Lin Gu, et al. (2019). Therapeutic outcomes in non-small cell lung cancer with BRAF mutations: a single institution, retrospective cohort study. Translational lung cancer research, 8(3). pp. 258–267. 10.21037/tlcr.2019.04.03 Retrieved from https://hdl.handle.net/10161/30086.

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Scholars@Duke

Ready

Neal Edward Ready

Professor of Medicine
Crawford

Jeffrey Crawford

George Barth Geller Distinguished Professor for Research in Cancer
  1. Lung cancer/new treatment approaches.
    2. Clinical trials of hematopoietic growth factors, biological agents and targeted drug development.
    3. Cancer in the elderly and supportive care

    Accomplishments

    1. Lead Investigator of the U. S. multicenter, randomized trial of Filgrastim (G-CSF, Neupogen) to reduce the morbidity of chemotherapy-related neutropenia, leading to FDA approval 2/91.
    2. Lead Investigator of the U. S. multicenter, randomized trial of Vinorelbine (Navelbine) in treatment of patients with advanced non small cell carcinoma of lung (NSCLC), leading to FDA approval 12/94.
    3. Principal Investigator in initial phase I clinical trials of stem cell factor (SCF), megakaryocyte growth and development factor (MGDF), pegylated granulocyte-colony-stimulating factor and other novel hematopoietic growth factors.
Datto

Michael Bradley Datto

Associate Professor of Pathology

Dr. Datto is an AP/CP/MGP board certified pathologist who specializes in molecular pathology. He is the Associate Vice President for Duke University Health System Clinical Laboratories, the Vice Chair for Clinical Pathology and Medical Director for Duke University Health System Clinical Laboratories.  

In these roles, he is responsible for maintaining the standards of the College of American Pathologists and CLIA/CMS within all Clinical Laboratories at Duke.  Specifically, Dr. Datto oversees clinical testing and reporting, develops quality management systems and proficiency testing programs, provides consultation with ordering physicians, ensures educational programs, develops strategic plans that are in line with the needs of our patient population, physicians and health system leadership, coordinates research and development, ensures adequate and appropriately trained personnel, and provides profession interpretation for molecular diagnostic testing including the wide range of PCR, quantitative PCR, sequencing and FISH based tests for inherited genetic diseases, hematologic malignancies, solid tumors and infectious diseases.

Dr. Datto also serves as the chair of the Accreditation Committee (AC) for the College of American Pathologists (CAP).  The CAP is the largest accreditor of hospital based laboratories in the US and serves as a ‘deemed entity’ by the Center for Medicare Services. In his role of chair of the AC, Dr. Datto oversees the committee that makes clinical accreditation decisions for approximately 7,000 clinical domestic and international laboratories.

Finally, Dr. Datto has an active academic program developing data system to aggregate, normalize and utilize high complexity and high volume laboratory data.  Dr. Datto and his team have developed the Molecular Registry of Tumors (Mr.T); a software solution that supports clinical trials matching, engagement with the AACR GENIE Project and the Molecular Tumor Board for Duke University Health System.  The ultimate goal of this work is to ensure that the vast amount of laboratory data generated on our Duke patients can be put to use, driving better patient care, research and education.

Clarke

Jeffrey Melson Clarke

Associate Professor of Medicine

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