Clinical characteristics and course of 63 patients with BRAF mutant lung cancers

Anya M. Litvak, Paul K. Paik, Kaitlin M. Woo, Camelia S. Sima, Matthew D. Hellmann, Maria E. Arcila, Marc Ladanyi, Charles M. Rudin, Mark G. Kris, Gregory J. Riely

Research output: Contribution to journalArticle

Abstract

Introduction: Mutant BRAF is a driver oncogene found in 2% of lung adenocarcinomas and represents a target for therapy. We examined the clinical characteristics and course of patients with lung adenocarcinomas harboring BRAF mutations. Methods: We identified patients with lung adenocarcinomas harboring BRAF mutations between 2009 and 2013 detected using a mass spectrometry-based polymerase chain reaction genotyping assay of hot-spot mutations involving codons corresponding to amino acids V600, D594, and G469 of BRAF. Patient characteristics and treatment outcomes were analyzed. Overall survival (OS) was compared with stage-matched patients with KRAS and EGFR mutant lung adenocarcinomas. Results: Sixty-three patients were diagnosed with BRAF mutant lung adenocarcinomas between 2009 and 2013 (V600, 36; non-V600, 27). The majority of patients with BRAF mutations were smokers (92%), although patients with V600 mutations were more likely to be light/never-smokers compared with patients with non-V600 mutations (42% versus 11%; p = 0.007). Of the 32 patients with early-stage disease, six (19%; 95% confidence interval 7%-36%) developed second primary lung cancers harboring KRAS mutations. Patients with advanced V600 mutant lung adenocarcinomas had a better survival from diagnosis compared with those with non-V600 mutant lung adenocarcinomas (3-year OS: 24% versus 0%; p <0.001). Conclusions: This is the largest series of patients with BRAF mutant lung cancers described. Most patients were heavy smokers. Nineteen percent of patients with early-stage BRAF mutant lung cancers developed second primary lung cancers harboring KRAS mutations. Patients with advanced lung adenocarcinomas harboring V600 mutations have an improved OS compared with those with non-V600 mutations.

Original languageEnglish (US)
Pages (from-to)1669-1674
Number of pages6
JournalJournal of Thoracic Oncology
Volume9
Issue number11
DOIs
StatePublished - Nov 1 2014
Externally publishedYes

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Lung Neoplasms
Mutation
Survival
Second Primary Neoplasms
Adenocarcinoma of lung
Oncogenes
Codon
Mass Spectrometry
Confidence Intervals
Light
Amino Acids
Polymerase Chain Reaction

Keywords

  • BRAF
  • Lung cancers
  • Non-small-cell lung cancers

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Litvak, A. M., Paik, P. K., Woo, K. M., Sima, C. S., Hellmann, M. D., Arcila, M. E., ... Riely, G. J. (2014). Clinical characteristics and course of 63 patients with BRAF mutant lung cancers. Journal of Thoracic Oncology, 9(11), 1669-1674. https://doi.org/10.1097/JTO.0000000000000344

Clinical characteristics and course of 63 patients with BRAF mutant lung cancers. / Litvak, Anya M.; Paik, Paul K.; Woo, Kaitlin M.; Sima, Camelia S.; Hellmann, Matthew D.; Arcila, Maria E.; Ladanyi, Marc; Rudin, Charles M.; Kris, Mark G.; Riely, Gregory J.

In: Journal of Thoracic Oncology, Vol. 9, No. 11, 01.11.2014, p. 1669-1674.

Research output: Contribution to journalArticle

Litvak, AM, Paik, PK, Woo, KM, Sima, CS, Hellmann, MD, Arcila, ME, Ladanyi, M, Rudin, CM, Kris, MG & Riely, GJ 2014, 'Clinical characteristics and course of 63 patients with BRAF mutant lung cancers', Journal of Thoracic Oncology, vol. 9, no. 11, pp. 1669-1674. https://doi.org/10.1097/JTO.0000000000000344
Litvak, Anya M. ; Paik, Paul K. ; Woo, Kaitlin M. ; Sima, Camelia S. ; Hellmann, Matthew D. ; Arcila, Maria E. ; Ladanyi, Marc ; Rudin, Charles M. ; Kris, Mark G. ; Riely, Gregory J. / Clinical characteristics and course of 63 patients with BRAF mutant lung cancers. In: Journal of Thoracic Oncology. 2014 ; Vol. 9, No. 11. pp. 1669-1674.
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abstract = "Introduction: Mutant BRAF is a driver oncogene found in 2{\%} of lung adenocarcinomas and represents a target for therapy. We examined the clinical characteristics and course of patients with lung adenocarcinomas harboring BRAF mutations. Methods: We identified patients with lung adenocarcinomas harboring BRAF mutations between 2009 and 2013 detected using a mass spectrometry-based polymerase chain reaction genotyping assay of hot-spot mutations involving codons corresponding to amino acids V600, D594, and G469 of BRAF. Patient characteristics and treatment outcomes were analyzed. Overall survival (OS) was compared with stage-matched patients with KRAS and EGFR mutant lung adenocarcinomas. Results: Sixty-three patients were diagnosed with BRAF mutant lung adenocarcinomas between 2009 and 2013 (V600, 36; non-V600, 27). The majority of patients with BRAF mutations were smokers (92{\%}), although patients with V600 mutations were more likely to be light/never-smokers compared with patients with non-V600 mutations (42{\%} versus 11{\%}; p = 0.007). Of the 32 patients with early-stage disease, six (19{\%}; 95{\%} confidence interval 7{\%}-36{\%}) developed second primary lung cancers harboring KRAS mutations. Patients with advanced V600 mutant lung adenocarcinomas had a better survival from diagnosis compared with those with non-V600 mutant lung adenocarcinomas (3-year OS: 24{\%} versus 0{\%}; p <0.001). Conclusions: This is the largest series of patients with BRAF mutant lung cancers described. Most patients were heavy smokers. Nineteen percent of patients with early-stage BRAF mutant lung cancers developed second primary lung cancers harboring KRAS mutations. Patients with advanced lung adenocarcinomas harboring V600 mutations have an improved OS compared with those with non-V600 mutations.",
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T1 - Clinical characteristics and course of 63 patients with BRAF mutant lung cancers

AU - Litvak, Anya M.

AU - Paik, Paul K.

AU - Woo, Kaitlin M.

AU - Sima, Camelia S.

AU - Hellmann, Matthew D.

AU - Arcila, Maria E.

AU - Ladanyi, Marc

AU - Rudin, Charles M.

AU - Kris, Mark G.

AU - Riely, Gregory J.

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N2 - Introduction: Mutant BRAF is a driver oncogene found in 2% of lung adenocarcinomas and represents a target for therapy. We examined the clinical characteristics and course of patients with lung adenocarcinomas harboring BRAF mutations. Methods: We identified patients with lung adenocarcinomas harboring BRAF mutations between 2009 and 2013 detected using a mass spectrometry-based polymerase chain reaction genotyping assay of hot-spot mutations involving codons corresponding to amino acids V600, D594, and G469 of BRAF. Patient characteristics and treatment outcomes were analyzed. Overall survival (OS) was compared with stage-matched patients with KRAS and EGFR mutant lung adenocarcinomas. Results: Sixty-three patients were diagnosed with BRAF mutant lung adenocarcinomas between 2009 and 2013 (V600, 36; non-V600, 27). The majority of patients with BRAF mutations were smokers (92%), although patients with V600 mutations were more likely to be light/never-smokers compared with patients with non-V600 mutations (42% versus 11%; p = 0.007). Of the 32 patients with early-stage disease, six (19%; 95% confidence interval 7%-36%) developed second primary lung cancers harboring KRAS mutations. Patients with advanced V600 mutant lung adenocarcinomas had a better survival from diagnosis compared with those with non-V600 mutant lung adenocarcinomas (3-year OS: 24% versus 0%; p <0.001). Conclusions: This is the largest series of patients with BRAF mutant lung cancers described. Most patients were heavy smokers. Nineteen percent of patients with early-stage BRAF mutant lung cancers developed second primary lung cancers harboring KRAS mutations. Patients with advanced lung adenocarcinomas harboring V600 mutations have an improved OS compared with those with non-V600 mutations.

AB - Introduction: Mutant BRAF is a driver oncogene found in 2% of lung adenocarcinomas and represents a target for therapy. We examined the clinical characteristics and course of patients with lung adenocarcinomas harboring BRAF mutations. Methods: We identified patients with lung adenocarcinomas harboring BRAF mutations between 2009 and 2013 detected using a mass spectrometry-based polymerase chain reaction genotyping assay of hot-spot mutations involving codons corresponding to amino acids V600, D594, and G469 of BRAF. Patient characteristics and treatment outcomes were analyzed. Overall survival (OS) was compared with stage-matched patients with KRAS and EGFR mutant lung adenocarcinomas. Results: Sixty-three patients were diagnosed with BRAF mutant lung adenocarcinomas between 2009 and 2013 (V600, 36; non-V600, 27). The majority of patients with BRAF mutations were smokers (92%), although patients with V600 mutations were more likely to be light/never-smokers compared with patients with non-V600 mutations (42% versus 11%; p = 0.007). Of the 32 patients with early-stage disease, six (19%; 95% confidence interval 7%-36%) developed second primary lung cancers harboring KRAS mutations. Patients with advanced V600 mutant lung adenocarcinomas had a better survival from diagnosis compared with those with non-V600 mutant lung adenocarcinomas (3-year OS: 24% versus 0%; p <0.001). Conclusions: This is the largest series of patients with BRAF mutant lung cancers described. Most patients were heavy smokers. Nineteen percent of patients with early-stage BRAF mutant lung cancers developed second primary lung cancers harboring KRAS mutations. Patients with advanced lung adenocarcinomas harboring V600 mutations have an improved OS compared with those with non-V600 mutations.

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KW - Lung cancers

KW - Non-small-cell lung cancers

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