Randomized, double-blinded, multicenter, phase II study of pemetrexed, carboplatin, and Bevacizumab with enzastaurin or placebo in chemonaïve patients with stage IIIB/IV non-small cell lung cancer

Hoosier oncology group LUN06-116

Erin M. Casey, Wael Harb, Daniel Bradford, Jose Bufill, Sreenivasa Nattam, Jyoti Patel, William Fisher, Jane E. Latz, Xiaochun Li, Jingwei Wu, Nasser Hanna

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Introduction: Bevacizumab is approved in combination with chemotherapy as first-line treatment for non-small cell lung cancer (NSCLC). Preclinical data suggest that enzastaurin and bevacizumab may have complementary effects in inhibiting angiogenesis. Methods: Eligibility criteria: ≥ 18 years of age, chemonaïve, stage IIIB/IV nonsquamous NSCLC, and Eastern Cooperative Oncology Group performance status 0 to 1. Patients were randomized to placebo or enzastaurin 500 mg orally daily (after a loading dose), plus pemetrexed 500 mg/m, carboplatin area under the curve 6, and bevacizumab 15 mg/kg, intravenously, every 21 days for four cycles. Patients without progression received maintenance therapy with bevacizumab and placebo or enzastaurin. The primary objective was progression-free survival (PFS). Planned sample size was 90 patients, one-sided alpha of 0.20, with two interim analyses: one for safety and the second for futility, with a PFS hazard ratio of 0.8857. Results: Forty patients were randomized. No unique safety concerns were noted at the first interim analysis. The early stopping rule for futility was met at the second interim analysis. Median PFS was 3.5 months and 4.3 months (hazard ratio: 1.04, 95% confidence interval: 0.49-2.21), and response rates were 20% and 30% (p = 0.462) for enzastaurin and placebo, respectively. Grade 3 or 4 toxicity was similar between the two arms. Two patients died on study because of respiratory arrest and pulmonary embolism. An additional patient died of sepsis secondary to a gastrointestinal perforation >30 days after study treatment discontinuation. Conclusions: Enzastaurin does not improve efficacy when combined with pemetrexed, carboplatin, and bevacizumab. This combination does not warrant further study in NSCLC.

Original languageEnglish
Pages (from-to)1815-1820
Number of pages6
JournalJournal of Thoracic Oncology
Volume5
Issue number11
DOIs
StatePublished - Nov 2010

Fingerprint

Pemetrexed
Carboplatin
Non-Small Cell Lung Carcinoma
Placebos
Medical Futility
Disease-Free Survival
Safety
Combination Drug Therapy
Pulmonary Embolism
Sample Size
Area Under Curve
Bevacizumab
enzastaurin
Sepsis
Therapeutics
Confidence Intervals

Keywords

  • Bevacizumab
  • Enzastaurin
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Randomized, double-blinded, multicenter, phase II study of pemetrexed, carboplatin, and Bevacizumab with enzastaurin or placebo in chemonaïve patients with stage IIIB/IV non-small cell lung cancer : Hoosier oncology group LUN06-116. / Casey, Erin M.; Harb, Wael; Bradford, Daniel; Bufill, Jose; Nattam, Sreenivasa; Patel, Jyoti; Fisher, William; Latz, Jane E.; Li, Xiaochun; Wu, Jingwei; Hanna, Nasser.

In: Journal of Thoracic Oncology, Vol. 5, No. 11, 11.2010, p. 1815-1820.

Research output: Contribution to journalArticle

Casey, Erin M. ; Harb, Wael ; Bradford, Daniel ; Bufill, Jose ; Nattam, Sreenivasa ; Patel, Jyoti ; Fisher, William ; Latz, Jane E. ; Li, Xiaochun ; Wu, Jingwei ; Hanna, Nasser. / Randomized, double-blinded, multicenter, phase II study of pemetrexed, carboplatin, and Bevacizumab with enzastaurin or placebo in chemonaïve patients with stage IIIB/IV non-small cell lung cancer : Hoosier oncology group LUN06-116. In: Journal of Thoracic Oncology. 2010 ; Vol. 5, No. 11. pp. 1815-1820.
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abstract = "Introduction: Bevacizumab is approved in combination with chemotherapy as first-line treatment for non-small cell lung cancer (NSCLC). Preclinical data suggest that enzastaurin and bevacizumab may have complementary effects in inhibiting angiogenesis. Methods: Eligibility criteria: ≥ 18 years of age, chemona{\"i}ve, stage IIIB/IV nonsquamous NSCLC, and Eastern Cooperative Oncology Group performance status 0 to 1. Patients were randomized to placebo or enzastaurin 500 mg orally daily (after a loading dose), plus pemetrexed 500 mg/m, carboplatin area under the curve 6, and bevacizumab 15 mg/kg, intravenously, every 21 days for four cycles. Patients without progression received maintenance therapy with bevacizumab and placebo or enzastaurin. The primary objective was progression-free survival (PFS). Planned sample size was 90 patients, one-sided alpha of 0.20, with two interim analyses: one for safety and the second for futility, with a PFS hazard ratio of 0.8857. Results: Forty patients were randomized. No unique safety concerns were noted at the first interim analysis. The early stopping rule for futility was met at the second interim analysis. Median PFS was 3.5 months and 4.3 months (hazard ratio: 1.04, 95{\%} confidence interval: 0.49-2.21), and response rates were 20{\%} and 30{\%} (p = 0.462) for enzastaurin and placebo, respectively. Grade 3 or 4 toxicity was similar between the two arms. Two patients died on study because of respiratory arrest and pulmonary embolism. An additional patient died of sepsis secondary to a gastrointestinal perforation >30 days after study treatment discontinuation. Conclusions: Enzastaurin does not improve efficacy when combined with pemetrexed, carboplatin, and bevacizumab. This combination does not warrant further study in NSCLC.",
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T1 - Randomized, double-blinded, multicenter, phase II study of pemetrexed, carboplatin, and Bevacizumab with enzastaurin or placebo in chemonaïve patients with stage IIIB/IV non-small cell lung cancer

T2 - Hoosier oncology group LUN06-116

AU - Casey, Erin M.

AU - Harb, Wael

AU - Bradford, Daniel

AU - Bufill, Jose

AU - Nattam, Sreenivasa

AU - Patel, Jyoti

AU - Fisher, William

AU - Latz, Jane E.

AU - Li, Xiaochun

AU - Wu, Jingwei

AU - Hanna, Nasser

PY - 2010/11

Y1 - 2010/11

N2 - Introduction: Bevacizumab is approved in combination with chemotherapy as first-line treatment for non-small cell lung cancer (NSCLC). Preclinical data suggest that enzastaurin and bevacizumab may have complementary effects in inhibiting angiogenesis. Methods: Eligibility criteria: ≥ 18 years of age, chemonaïve, stage IIIB/IV nonsquamous NSCLC, and Eastern Cooperative Oncology Group performance status 0 to 1. Patients were randomized to placebo or enzastaurin 500 mg orally daily (after a loading dose), plus pemetrexed 500 mg/m, carboplatin area under the curve 6, and bevacizumab 15 mg/kg, intravenously, every 21 days for four cycles. Patients without progression received maintenance therapy with bevacizumab and placebo or enzastaurin. The primary objective was progression-free survival (PFS). Planned sample size was 90 patients, one-sided alpha of 0.20, with two interim analyses: one for safety and the second for futility, with a PFS hazard ratio of 0.8857. Results: Forty patients were randomized. No unique safety concerns were noted at the first interim analysis. The early stopping rule for futility was met at the second interim analysis. Median PFS was 3.5 months and 4.3 months (hazard ratio: 1.04, 95% confidence interval: 0.49-2.21), and response rates were 20% and 30% (p = 0.462) for enzastaurin and placebo, respectively. Grade 3 or 4 toxicity was similar between the two arms. Two patients died on study because of respiratory arrest and pulmonary embolism. An additional patient died of sepsis secondary to a gastrointestinal perforation >30 days after study treatment discontinuation. Conclusions: Enzastaurin does not improve efficacy when combined with pemetrexed, carboplatin, and bevacizumab. This combination does not warrant further study in NSCLC.

AB - Introduction: Bevacizumab is approved in combination with chemotherapy as first-line treatment for non-small cell lung cancer (NSCLC). Preclinical data suggest that enzastaurin and bevacizumab may have complementary effects in inhibiting angiogenesis. Methods: Eligibility criteria: ≥ 18 years of age, chemonaïve, stage IIIB/IV nonsquamous NSCLC, and Eastern Cooperative Oncology Group performance status 0 to 1. Patients were randomized to placebo or enzastaurin 500 mg orally daily (after a loading dose), plus pemetrexed 500 mg/m, carboplatin area under the curve 6, and bevacizumab 15 mg/kg, intravenously, every 21 days for four cycles. Patients without progression received maintenance therapy with bevacizumab and placebo or enzastaurin. The primary objective was progression-free survival (PFS). Planned sample size was 90 patients, one-sided alpha of 0.20, with two interim analyses: one for safety and the second for futility, with a PFS hazard ratio of 0.8857. Results: Forty patients were randomized. No unique safety concerns were noted at the first interim analysis. The early stopping rule for futility was met at the second interim analysis. Median PFS was 3.5 months and 4.3 months (hazard ratio: 1.04, 95% confidence interval: 0.49-2.21), and response rates were 20% and 30% (p = 0.462) for enzastaurin and placebo, respectively. Grade 3 or 4 toxicity was similar between the two arms. Two patients died on study because of respiratory arrest and pulmonary embolism. An additional patient died of sepsis secondary to a gastrointestinal perforation >30 days after study treatment discontinuation. Conclusions: Enzastaurin does not improve efficacy when combined with pemetrexed, carboplatin, and bevacizumab. This combination does not warrant further study in NSCLC.

KW - Bevacizumab

KW - Enzastaurin

KW - Non-small cell lung cancer

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