EGFR mutations detected in plasma are associated with patient outcomes in erlotinib plus docetaxel-treated non-small cell lung cancer

Philip Mack, William S. Holland, Rebekah A. Burich, Randeep Sangha, Leslie J. Solis, Yueju Li, Laurel A Beckett, Primo N Lara, Angela M. Davies, David R Gandara

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Purpose:: Activating mutations in the epidermal growth factor receptor (EGFR) are associated with enhanced response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC), whereas KRAS mutations translate into poor patient outcomes. We hypothesized that analysis of plasma for EGFR and KRAS mutations from shed tumor DNA would have clinical utility. Methods: An allele-specific polymerase chain reaction assay using Scorpion-amplification refractory mutation system (DxS, Ltd) was used to detect mutations in plasma DNA from patients with advanced stage NSCLC treated as second- or third-line therapy on a phase I/II trial of docetaxel plus intercalated erlotinib. Results: EGFR mutations were detected in 10 of 49 patients (20%). Six (12%) had single activating mutations in EGFR, associated with improved progression-free survival (median, 18.3 months), compared with all other patients (median, 3.9 months; p = 0.008), or those with wild-type EGFR (median, 4.0 months; p = 0.012). Four of 49 patients harbored a de novo T790M resistance mutation (median progression-free survival, 3.9 months). EGFR mutational status was associated with clinical response (45 assessable, p = 0.0001); in the six patients with activating mutations, all achieved complete (33%) or partial (67%) response. All CR patients had E19del detectable in both tumor and plasma. KRAS mutations were detected in two of 49 (4%) patients, both of whom had rapid progressive disease. Conclusions: Activating EGFR mutations detected in shed DNA in plasma are significantly associated with favorable outcomes in patients with advanced NSCLC receiving docetaxel plus intercalated erlotinib. The addition of docetaxel in this schedule did not diminish the efficacy of erlotinib against patients with EGFR activating mutations.

Original languageEnglish (US)
Pages (from-to)1466-1472
Number of pages7
JournalJournal of Thoracic Oncology
Volume4
Issue number12
DOIs
StatePublished - Dec 2009

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docetaxel
Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Mutation
Disease-Free Survival
Erlotinib Hydrochloride
DNA
Scorpions

Keywords

  • EGFR
  • Erlotinib
  • NSCLC
  • Plasma

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

EGFR mutations detected in plasma are associated with patient outcomes in erlotinib plus docetaxel-treated non-small cell lung cancer. / Mack, Philip; Holland, William S.; Burich, Rebekah A.; Sangha, Randeep; Solis, Leslie J.; Li, Yueju; Beckett, Laurel A; Lara, Primo N; Davies, Angela M.; Gandara, David R.

In: Journal of Thoracic Oncology, Vol. 4, No. 12, 12.2009, p. 1466-1472.

Research output: Contribution to journalArticle

Mack, Philip ; Holland, William S. ; Burich, Rebekah A. ; Sangha, Randeep ; Solis, Leslie J. ; Li, Yueju ; Beckett, Laurel A ; Lara, Primo N ; Davies, Angela M. ; Gandara, David R. / EGFR mutations detected in plasma are associated with patient outcomes in erlotinib plus docetaxel-treated non-small cell lung cancer. In: Journal of Thoracic Oncology. 2009 ; Vol. 4, No. 12. pp. 1466-1472.
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title = "EGFR mutations detected in plasma are associated with patient outcomes in erlotinib plus docetaxel-treated non-small cell lung cancer",
abstract = "Purpose:: Activating mutations in the epidermal growth factor receptor (EGFR) are associated with enhanced response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC), whereas KRAS mutations translate into poor patient outcomes. We hypothesized that analysis of plasma for EGFR and KRAS mutations from shed tumor DNA would have clinical utility. Methods: An allele-specific polymerase chain reaction assay using Scorpion-amplification refractory mutation system (DxS, Ltd) was used to detect mutations in plasma DNA from patients with advanced stage NSCLC treated as second- or third-line therapy on a phase I/II trial of docetaxel plus intercalated erlotinib. Results: EGFR mutations were detected in 10 of 49 patients (20{\%}). Six (12{\%}) had single activating mutations in EGFR, associated with improved progression-free survival (median, 18.3 months), compared with all other patients (median, 3.9 months; p = 0.008), or those with wild-type EGFR (median, 4.0 months; p = 0.012). Four of 49 patients harbored a de novo T790M resistance mutation (median progression-free survival, 3.9 months). EGFR mutational status was associated with clinical response (45 assessable, p = 0.0001); in the six patients with activating mutations, all achieved complete (33{\%}) or partial (67{\%}) response. All CR patients had E19del detectable in both tumor and plasma. KRAS mutations were detected in two of 49 (4{\%}) patients, both of whom had rapid progressive disease. Conclusions: Activating EGFR mutations detected in shed DNA in plasma are significantly associated with favorable outcomes in patients with advanced NSCLC receiving docetaxel plus intercalated erlotinib. The addition of docetaxel in this schedule did not diminish the efficacy of erlotinib against patients with EGFR activating mutations.",
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T1 - EGFR mutations detected in plasma are associated with patient outcomes in erlotinib plus docetaxel-treated non-small cell lung cancer

AU - Mack, Philip

AU - Holland, William S.

AU - Burich, Rebekah A.

AU - Sangha, Randeep

AU - Solis, Leslie J.

AU - Li, Yueju

AU - Beckett, Laurel A

AU - Lara, Primo N

AU - Davies, Angela M.

AU - Gandara, David R

PY - 2009/12

Y1 - 2009/12

N2 - Purpose:: Activating mutations in the epidermal growth factor receptor (EGFR) are associated with enhanced response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC), whereas KRAS mutations translate into poor patient outcomes. We hypothesized that analysis of plasma for EGFR and KRAS mutations from shed tumor DNA would have clinical utility. Methods: An allele-specific polymerase chain reaction assay using Scorpion-amplification refractory mutation system (DxS, Ltd) was used to detect mutations in plasma DNA from patients with advanced stage NSCLC treated as second- or third-line therapy on a phase I/II trial of docetaxel plus intercalated erlotinib. Results: EGFR mutations were detected in 10 of 49 patients (20%). Six (12%) had single activating mutations in EGFR, associated with improved progression-free survival (median, 18.3 months), compared with all other patients (median, 3.9 months; p = 0.008), or those with wild-type EGFR (median, 4.0 months; p = 0.012). Four of 49 patients harbored a de novo T790M resistance mutation (median progression-free survival, 3.9 months). EGFR mutational status was associated with clinical response (45 assessable, p = 0.0001); in the six patients with activating mutations, all achieved complete (33%) or partial (67%) response. All CR patients had E19del detectable in both tumor and plasma. KRAS mutations were detected in two of 49 (4%) patients, both of whom had rapid progressive disease. Conclusions: Activating EGFR mutations detected in shed DNA in plasma are significantly associated with favorable outcomes in patients with advanced NSCLC receiving docetaxel plus intercalated erlotinib. The addition of docetaxel in this schedule did not diminish the efficacy of erlotinib against patients with EGFR activating mutations.

AB - Purpose:: Activating mutations in the epidermal growth factor receptor (EGFR) are associated with enhanced response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC), whereas KRAS mutations translate into poor patient outcomes. We hypothesized that analysis of plasma for EGFR and KRAS mutations from shed tumor DNA would have clinical utility. Methods: An allele-specific polymerase chain reaction assay using Scorpion-amplification refractory mutation system (DxS, Ltd) was used to detect mutations in plasma DNA from patients with advanced stage NSCLC treated as second- or third-line therapy on a phase I/II trial of docetaxel plus intercalated erlotinib. Results: EGFR mutations were detected in 10 of 49 patients (20%). Six (12%) had single activating mutations in EGFR, associated with improved progression-free survival (median, 18.3 months), compared with all other patients (median, 3.9 months; p = 0.008), or those with wild-type EGFR (median, 4.0 months; p = 0.012). Four of 49 patients harbored a de novo T790M resistance mutation (median progression-free survival, 3.9 months). EGFR mutational status was associated with clinical response (45 assessable, p = 0.0001); in the six patients with activating mutations, all achieved complete (33%) or partial (67%) response. All CR patients had E19del detectable in both tumor and plasma. KRAS mutations were detected in two of 49 (4%) patients, both of whom had rapid progressive disease. Conclusions: Activating EGFR mutations detected in shed DNA in plasma are significantly associated with favorable outcomes in patients with advanced NSCLC receiving docetaxel plus intercalated erlotinib. The addition of docetaxel in this schedule did not diminish the efficacy of erlotinib against patients with EGFR activating mutations.

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KW - Erlotinib

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