Paired Phase II Studies of Erlotinib/Bevacizumab for Advanced Bronchioloalveolar Carcinoma or Never Smokers With Advanced Non-Small-cell Lung Cancer: SWOG S0635 and S0636 Trials

Howard L. West, James Moon, Antoinette J. Wozniak, Philip Mack, Fred R. Hirsch, Martin J. Bury, Myron Kwong, Dorothy D. Nguyen, Dennis F. Moore, Jieling Miao, Mary Redman, Karen Kelly, David R Gandara

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636). Materials and Methods: Eligible patients with BAC or adenocarcinoma with BAC features (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636) received erlotinib 150 mg/day with bevacizumab 15 mg/kg until progression or prohibitive toxicity. Never smokers with BAC were preferentially enrolled to SWOG S0636. The primary endpoint for both trials was overall survival. Results: A total of 84 patients were enrolled in the SWOG S0635 trial and 85 in the SWOG S0636 trial. The objective response rate was 22% (3% complete response) in the SWOG S0635 trial and 50% (38% confirmed; 3% complete response) in the SWOG S0636 trial. The median progression-free survival was 5 and 7.4 months in the S0635 and S0636 trials, respectively. The median overall survival was 21 and 29.8 months, respectively. Toxicity consisted mainly of rash and diarrhea in both trials. Conclusion: Although the field has moved toward molecular, rather than clinical, selection of patients as optimal candidates for EGFR TKI therapy, these results support the hypothesis that a subset of patients in whom erlotinib is particularly active could receive an incremental benefit from the addition of bevacizumab.

Original languageEnglish (US)
JournalClinical Lung Cancer
DOIs
StateAccepted/In press - 2017

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Bronchiolo-Alveolar Adenocarcinoma
Non-Small Cell Lung Carcinoma
Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
erbB-1 Genes
Angiogenesis Inhibitors
Survival
Exanthema
Patient Selection
Disease-Free Survival
Diarrhea
Adenocarcinoma
Bevacizumab
Erlotinib Hydrochloride
Mutation
Population

Keywords

  • Antiangiogenesis
  • BAC
  • Bronchioloalveolar
  • EGFR
  • Lepidic
  • Never-smoker

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Paired Phase II Studies of Erlotinib/Bevacizumab for Advanced Bronchioloalveolar Carcinoma or Never Smokers With Advanced Non-Small-cell Lung Cancer : SWOG S0635 and S0636 Trials. / West, Howard L.; Moon, James; Wozniak, Antoinette J.; Mack, Philip; Hirsch, Fred R.; Bury, Martin J.; Kwong, Myron; Nguyen, Dorothy D.; Moore, Dennis F.; Miao, Jieling; Redman, Mary; Kelly, Karen; Gandara, David R.

In: Clinical Lung Cancer, 2017.

Research output: Contribution to journalArticle

West, Howard L. ; Moon, James ; Wozniak, Antoinette J. ; Mack, Philip ; Hirsch, Fred R. ; Bury, Martin J. ; Kwong, Myron ; Nguyen, Dorothy D. ; Moore, Dennis F. ; Miao, Jieling ; Redman, Mary ; Kelly, Karen ; Gandara, David R. / Paired Phase II Studies of Erlotinib/Bevacizumab for Advanced Bronchioloalveolar Carcinoma or Never Smokers With Advanced Non-Small-cell Lung Cancer : SWOG S0635 and S0636 Trials. In: Clinical Lung Cancer. 2017.
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title = "Paired Phase II Studies of Erlotinib/Bevacizumab for Advanced Bronchioloalveolar Carcinoma or Never Smokers With Advanced Non-Small-cell Lung Cancer: SWOG S0635 and S0636 Trials",
abstract = "Background: Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636). Materials and Methods: Eligible patients with BAC or adenocarcinoma with BAC features (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636) received erlotinib 150 mg/day with bevacizumab 15 mg/kg until progression or prohibitive toxicity. Never smokers with BAC were preferentially enrolled to SWOG S0636. The primary endpoint for both trials was overall survival. Results: A total of 84 patients were enrolled in the SWOG S0635 trial and 85 in the SWOG S0636 trial. The objective response rate was 22{\%} (3{\%} complete response) in the SWOG S0635 trial and 50{\%} (38{\%} confirmed; 3{\%} complete response) in the SWOG S0636 trial. The median progression-free survival was 5 and 7.4 months in the S0635 and S0636 trials, respectively. The median overall survival was 21 and 29.8 months, respectively. Toxicity consisted mainly of rash and diarrhea in both trials. Conclusion: Although the field has moved toward molecular, rather than clinical, selection of patients as optimal candidates for EGFR TKI therapy, these results support the hypothesis that a subset of patients in whom erlotinib is particularly active could receive an incremental benefit from the addition of bevacizumab.",
keywords = "Antiangiogenesis, BAC, Bronchioloalveolar, EGFR, Lepidic, Never-smoker",
author = "West, {Howard L.} and James Moon and Wozniak, {Antoinette J.} and Philip Mack and Hirsch, {Fred R.} and Bury, {Martin J.} and Myron Kwong and Nguyen, {Dorothy D.} and Moore, {Dennis F.} and Jieling Miao and Mary Redman and Karen Kelly and Gandara, {David R}",
year = "2017",
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journal = "Clinical Lung Cancer",
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T1 - Paired Phase II Studies of Erlotinib/Bevacizumab for Advanced Bronchioloalveolar Carcinoma or Never Smokers With Advanced Non-Small-cell Lung Cancer

T2 - SWOG S0635 and S0636 Trials

AU - West, Howard L.

AU - Moon, James

AU - Wozniak, Antoinette J.

AU - Mack, Philip

AU - Hirsch, Fred R.

AU - Bury, Martin J.

AU - Kwong, Myron

AU - Nguyen, Dorothy D.

AU - Moore, Dennis F.

AU - Miao, Jieling

AU - Redman, Mary

AU - Kelly, Karen

AU - Gandara, David R

PY - 2017

Y1 - 2017

N2 - Background: Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636). Materials and Methods: Eligible patients with BAC or adenocarcinoma with BAC features (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636) received erlotinib 150 mg/day with bevacizumab 15 mg/kg until progression or prohibitive toxicity. Never smokers with BAC were preferentially enrolled to SWOG S0636. The primary endpoint for both trials was overall survival. Results: A total of 84 patients were enrolled in the SWOG S0635 trial and 85 in the SWOG S0636 trial. The objective response rate was 22% (3% complete response) in the SWOG S0635 trial and 50% (38% confirmed; 3% complete response) in the SWOG S0636 trial. The median progression-free survival was 5 and 7.4 months in the S0635 and S0636 trials, respectively. The median overall survival was 21 and 29.8 months, respectively. Toxicity consisted mainly of rash and diarrhea in both trials. Conclusion: Although the field has moved toward molecular, rather than clinical, selection of patients as optimal candidates for EGFR TKI therapy, these results support the hypothesis that a subset of patients in whom erlotinib is particularly active could receive an incremental benefit from the addition of bevacizumab.

AB - Background: Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636). Materials and Methods: Eligible patients with BAC or adenocarcinoma with BAC features (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636) received erlotinib 150 mg/day with bevacizumab 15 mg/kg until progression or prohibitive toxicity. Never smokers with BAC were preferentially enrolled to SWOG S0636. The primary endpoint for both trials was overall survival. Results: A total of 84 patients were enrolled in the SWOG S0635 trial and 85 in the SWOG S0636 trial. The objective response rate was 22% (3% complete response) in the SWOG S0635 trial and 50% (38% confirmed; 3% complete response) in the SWOG S0636 trial. The median progression-free survival was 5 and 7.4 months in the S0635 and S0636 trials, respectively. The median overall survival was 21 and 29.8 months, respectively. Toxicity consisted mainly of rash and diarrhea in both trials. Conclusion: Although the field has moved toward molecular, rather than clinical, selection of patients as optimal candidates for EGFR TKI therapy, these results support the hypothesis that a subset of patients in whom erlotinib is particularly active could receive an incremental benefit from the addition of bevacizumab.

KW - Antiangiogenesis

KW - BAC

KW - Bronchioloalveolar

KW - EGFR

KW - Lepidic

KW - Never-smoker

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