Phase II trial of carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab in advanced nonsquamous non-small-cell lung cancer SWOG S0536

Edward S. Kim, James Moon, Roy S. Herbst, Mary W. Redman, Shaker R. Dakhil, Mario R. Velasco, Fred R. Hirsch, Philip Mack, Karen Kelly, John V. Heymach, David R Gandara

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Introduction: Cetuximab and bevacizumab have each been demonstrated to prolong survival when added to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). However, the potential benefit of combining cetuximab and bevacizumab together with a platinum-based doublet had not been explored. We designed this phase II trial to evaluate the safety, tolerability, and efficacy of the combination of carboplatin, paclitaxel, cetuximab, and bevacizumab in chemotherapy-naive patients with advanced, nonsquamous NSCLC. Methods: Patients received with up to six cycles of carboplatin (area under curve 6), paclitaxel (200 mg/m2), cetuximab (400 mg/m2 day 1 then 250 mg/m2 weekly), and bevacizumab (15 mg/kg) every 21 days. Patients with an objective response or stable disease received maintenance cetuximab (250 mg/m2 weekly) and bevacizumab (15 mg/kg every 21 days) until disease progression. The primary endpoint was safety as defined by the frequency and severity of hemorrhagic toxicities. Secondary endpoints included response rate, progression-free survival, overall survival, and toxicity. Molecular biomarkers were assessed in an exploratory manner. Results: The primary endpoint of grade 4 or higher hemorrhage of 2% (95% confidence interval: 0%-7%) met prespecified criteria for safety. One hundred ten patients were enrolled. There were four treatment-related deaths including lung hemorrhage (2), infection (1), and unknown (1). Median progression-free survival was 7 months and median overall survival was 15 months. The response rate was 56% with an overall disease control rate of 77%. Conclusion: This regimen was safe, feasible, and effective as a frontline treatment of advanced NSCLC, providing the basis for the ongoing phase III trial S0819.

Original languageEnglish (US)
Pages (from-to)1519-1528
Number of pages10
JournalJournal of Thoracic Oncology
Volume8
Issue number12
DOIs
StatePublished - 2013

Fingerprint

Carboplatin
Paclitaxel
Non-Small Cell Lung Carcinoma
Safety
Disease-Free Survival
Survival
Hemorrhage
Drug Therapy
Platinum
Area Under Curve
Disease Progression
Biomarkers
Maintenance
Cetuximab
Bevacizumab
Confidence Intervals
Lung
Therapeutics
Infection

Keywords

  • Bevacizumab
  • Carboplatin
  • Cetuximab
  • Frontline
  • Non-small-cell lung cancer
  • Paclitaxel

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Phase II trial of carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab in advanced nonsquamous non-small-cell lung cancer SWOG S0536. / Kim, Edward S.; Moon, James; Herbst, Roy S.; Redman, Mary W.; Dakhil, Shaker R.; Velasco, Mario R.; Hirsch, Fred R.; Mack, Philip; Kelly, Karen; Heymach, John V.; Gandara, David R.

In: Journal of Thoracic Oncology, Vol. 8, No. 12, 2013, p. 1519-1528.

Research output: Contribution to journalArticle

Kim, Edward S. ; Moon, James ; Herbst, Roy S. ; Redman, Mary W. ; Dakhil, Shaker R. ; Velasco, Mario R. ; Hirsch, Fred R. ; Mack, Philip ; Kelly, Karen ; Heymach, John V. ; Gandara, David R. / Phase II trial of carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab in advanced nonsquamous non-small-cell lung cancer SWOG S0536. In: Journal of Thoracic Oncology. 2013 ; Vol. 8, No. 12. pp. 1519-1528.
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abstract = "Introduction: Cetuximab and bevacizumab have each been demonstrated to prolong survival when added to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). However, the potential benefit of combining cetuximab and bevacizumab together with a platinum-based doublet had not been explored. We designed this phase II trial to evaluate the safety, tolerability, and efficacy of the combination of carboplatin, paclitaxel, cetuximab, and bevacizumab in chemotherapy-naive patients with advanced, nonsquamous NSCLC. Methods: Patients received with up to six cycles of carboplatin (area under curve 6), paclitaxel (200 mg/m2), cetuximab (400 mg/m2 day 1 then 250 mg/m2 weekly), and bevacizumab (15 mg/kg) every 21 days. Patients with an objective response or stable disease received maintenance cetuximab (250 mg/m2 weekly) and bevacizumab (15 mg/kg every 21 days) until disease progression. The primary endpoint was safety as defined by the frequency and severity of hemorrhagic toxicities. Secondary endpoints included response rate, progression-free survival, overall survival, and toxicity. Molecular biomarkers were assessed in an exploratory manner. Results: The primary endpoint of grade 4 or higher hemorrhage of 2{\%} (95{\%} confidence interval: 0{\%}-7{\%}) met prespecified criteria for safety. One hundred ten patients were enrolled. There were four treatment-related deaths including lung hemorrhage (2), infection (1), and unknown (1). Median progression-free survival was 7 months and median overall survival was 15 months. The response rate was 56{\%} with an overall disease control rate of 77{\%}. Conclusion: This regimen was safe, feasible, and effective as a frontline treatment of advanced NSCLC, providing the basis for the ongoing phase III trial S0819.",
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T1 - Phase II trial of carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab in advanced nonsquamous non-small-cell lung cancer SWOG S0536

AU - Kim, Edward S.

AU - Moon, James

AU - Herbst, Roy S.

AU - Redman, Mary W.

AU - Dakhil, Shaker R.

AU - Velasco, Mario R.

AU - Hirsch, Fred R.

AU - Mack, Philip

AU - Kelly, Karen

AU - Heymach, John V.

AU - Gandara, David R

PY - 2013

Y1 - 2013

N2 - Introduction: Cetuximab and bevacizumab have each been demonstrated to prolong survival when added to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). However, the potential benefit of combining cetuximab and bevacizumab together with a platinum-based doublet had not been explored. We designed this phase II trial to evaluate the safety, tolerability, and efficacy of the combination of carboplatin, paclitaxel, cetuximab, and bevacizumab in chemotherapy-naive patients with advanced, nonsquamous NSCLC. Methods: Patients received with up to six cycles of carboplatin (area under curve 6), paclitaxel (200 mg/m2), cetuximab (400 mg/m2 day 1 then 250 mg/m2 weekly), and bevacizumab (15 mg/kg) every 21 days. Patients with an objective response or stable disease received maintenance cetuximab (250 mg/m2 weekly) and bevacizumab (15 mg/kg every 21 days) until disease progression. The primary endpoint was safety as defined by the frequency and severity of hemorrhagic toxicities. Secondary endpoints included response rate, progression-free survival, overall survival, and toxicity. Molecular biomarkers were assessed in an exploratory manner. Results: The primary endpoint of grade 4 or higher hemorrhage of 2% (95% confidence interval: 0%-7%) met prespecified criteria for safety. One hundred ten patients were enrolled. There were four treatment-related deaths including lung hemorrhage (2), infection (1), and unknown (1). Median progression-free survival was 7 months and median overall survival was 15 months. The response rate was 56% with an overall disease control rate of 77%. Conclusion: This regimen was safe, feasible, and effective as a frontline treatment of advanced NSCLC, providing the basis for the ongoing phase III trial S0819.

AB - Introduction: Cetuximab and bevacizumab have each been demonstrated to prolong survival when added to chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). However, the potential benefit of combining cetuximab and bevacizumab together with a platinum-based doublet had not been explored. We designed this phase II trial to evaluate the safety, tolerability, and efficacy of the combination of carboplatin, paclitaxel, cetuximab, and bevacizumab in chemotherapy-naive patients with advanced, nonsquamous NSCLC. Methods: Patients received with up to six cycles of carboplatin (area under curve 6), paclitaxel (200 mg/m2), cetuximab (400 mg/m2 day 1 then 250 mg/m2 weekly), and bevacizumab (15 mg/kg) every 21 days. Patients with an objective response or stable disease received maintenance cetuximab (250 mg/m2 weekly) and bevacizumab (15 mg/kg every 21 days) until disease progression. The primary endpoint was safety as defined by the frequency and severity of hemorrhagic toxicities. Secondary endpoints included response rate, progression-free survival, overall survival, and toxicity. Molecular biomarkers were assessed in an exploratory manner. Results: The primary endpoint of grade 4 or higher hemorrhage of 2% (95% confidence interval: 0%-7%) met prespecified criteria for safety. One hundred ten patients were enrolled. There were four treatment-related deaths including lung hemorrhage (2), infection (1), and unknown (1). Median progression-free survival was 7 months and median overall survival was 15 months. The response rate was 56% with an overall disease control rate of 77%. Conclusion: This regimen was safe, feasible, and effective as a frontline treatment of advanced NSCLC, providing the basis for the ongoing phase III trial S0819.

KW - Bevacizumab

KW - Carboplatin

KW - Cetuximab

KW - Frontline

KW - Non-small-cell lung cancer

KW - Paclitaxel

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