Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib Journal Article

Authors: Miller, V. A.; Riely, G. J.; Zakowski, M. F.; Li, A. R.; Patel, J. D.; Heelan, R. T.; Kris, M. G.; Sandler, A. B.; Carbone, D. P.; Tsao, A.; Herbst, R. S.; Heller, G.; Ladanyi, M.; Pao, W.; Johnson, D. H.
Article Title: Molecular characteristics of bronchioloalveolar carcinoma and adenocarcinoma, bronchioloalveolar carcinoma subtype, predict response to erlotinib
Abstract: Purpose: We conducted this phase II trial to determine the efficacy of erlotinib in patients with bronchioloalveolar carcinoma (BAC) and adenocarcinoma, BAC subtype, and to determine molecular characteristics associated with response. Patients and Methods: Patients (n = 101) with BAC (n = 12) or adenocarcinoma, BAC subtype (n = 89), were enrolled. All patients received erlotinib 150 mg daily. Epidermal growth factor receptor (EGFR) mutation, EGFR copy number, EGFR immunohistochemistry (IHC), and KRAS mutation status were analyzed in available tumors. The primary end point was response rate (RR). Results: Overall RR was 22% (95% CI, 14% to 31%). In patients with pure BAC, the RR and median survival were 20% and 4 months, as compared with 23% and 19 months in those with adenocarcinoma, BAC subtype. No patient (zero of 18; 95% CI, 0% to 19%) whose tumor harbored a KRAS mutation responded to erlotinib. Patients with EGFR mutations had an 83% RR (15 of 18; 95% CI, 65% to 94%) and 23-month median OS. On univariate analysis, EGFR mutation and copy number were associated with RR and PFS. EGFR IHC was not associated with RR or progression-free survival (PFS). After multivariate analysis, only EGFR mutation was associated with RR and PFS. No molecular factors were associated with overall survival. Conclusion: Erlotinib is active in BAC and adenocarcinoma, mixed subtype, BAC. Testing for EGFR and KRAS mutations can predict RR and PFS after treatment with erlotinib in this histologically enriched subset of patients with non-small-cell lung cancer (NSCLC). These data suggest that histologic subtype and molecular characteristics should be reported in clinical trials in NSCLC using EGFR-directed therapy. © 2008 by American Society of Clinical Oncology.
Keywords: immunohistochemistry; adult; cancer survival; human tissue; treatment outcome; treatment response; aged; aged, 80 and over; disease-free survival; middle aged; unclassified drug; oncoprotein; gene mutation; major clinical study; genetics; mutation; proto-oncogene proteins; clinical trial; erlotinib; drug efficacy; antineoplastic agents; cancer patient; disease free survival; antineoplastic agent; adenocarcinoma; metabolism; progression free survival; multiple cycle treatment; phase 2 clinical trial; protein kinase inhibitor; lung non small cell cancer; lung neoplasms; epidermal growth factor receptor; tumor markers, biological; receptor, epidermal growth factor; tumor marker; protein kinase inhibitors; lung tumor; lung adenocarcinoma; multicenter study; lung alveolus cell carcinoma; ras protein; multivariate analysis; ras proteins; egfr gene; oncogene k ras; quinazolines; univariate analysis; quinazoline derivative; receptor gene; kras protein, human; adenocarcinoma, bronchiolo-alveolar; cytokine inducible sh2 containing protein; cytokine inducible sh2-containing protein; suppressor of cytokine signaling; suppressor of cytokine signaling proteins
Journal Title: Journal of Clinical Oncology
Volume: 26
Issue: 9
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2008-03-20
Start Page: 1472
End Page: 1478
Language: English
DOI: 10.1200/jco.2007.13.0062
PUBMED: 18349398
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 125" - "Export Date: 17 November 2011" - "CODEN: JCOND" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Glenn Heller
    295 Heller
  2. Vincent Miller
    262 Miller
  3. Marc Ladanyi
    864 Ladanyi
  4. Gregory J Riely
    344 Riely
  5. Maureen F Zakowski
    275 Zakowski
  6. Mark Kris
    598 Kris
  7. Robert T Heelan
    79 Heelan