A phase II study of enzastaurin in combination with erlotinib in patients with previously treated advanced non-small cell lung cancer

Christelle Clément-Duchêne; Ronald B. Natale; Thierry Jahan; Yelena Krupitskaya; Raymond Osarogiagbon; Rachel E. Sanborn; Eric D. Bernstein; Arkadiusz Z. Dudek; Jane E. Latz; Peipei Shi; Heather A. Wakelee

doi:10.1016/j.lungcan.2012.06.003

A phase II study of enzastaurin in combination with erlotinib in patients with previously treated advanced non-small cell lung cancer

Christelle Clément-Duchêne, Ronald B. Natale, Thierry Jahan, Yelena Krupitskaya, Raymond Osarogiagbon, Rachel E. Sanborn, Eric D. Bernstein, Arkadiusz Z. Dudek, Jane E. Latz, Peipei Shi, Heather A. Wakelee

Medicine - Hematology, Oncology, Transplant

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Introduction: Regardless of epidermal growth factor receptor (EGFR) mutation status, erlotinib improves survival for patients with advanced non-small cell lung cancer (NSCLC) after one or more chemotherapy regimens. Enzastaurin is an oral serine/threonine kinase inhibitor. This phase II study was designed to evaluate the efficacy and safety of erlotinib and enzastaurin in NSCLC, a combination with promise to overcome EGFR resistance based on preclinical models. Methods: Eligible patients with advanced NSCLC (IIIB or IV) who had failed one or two prior systemic treatment regimen(s) were enrolled and received erlotinib 150. mg/day and enzastaurin 500. mg/day (after a 1125-mg loading dose on day 1, cycle 1), both orally in 28-day cycles. The primary endpoint was progression-free survival (PFS). Results: From January 2008 to July 2009, 49 patients were enrolled: 29 (59%) men and 20 (41%) women; 8 (16%) were non-smokers. The median PFS was 1.7. months (one-sided 90% CI: 1.5-NA) and median overall survival (OS) was 8.3. months (95% CI: 5.3-14.3). Five patients had partial response, for an overall response rate of 10.2%; the disease control rate was 30.6% (responders. +. 10 patients with stable disease). Grade 3-4 drug-related adverse events in ≥5% of patients were diarrhea, acne, and nausea. One possibly drug-related death due to interstitial lung disease occurred during the study. Conclusions: In previously treated, unselected, advanced NSCLC patients, the addition of enzastaurin to erlotinib did not improve PFS, response, or OS compared with historical data of single-agent erlotinib, but was well tolerated.

Original language	English (US)
Pages (from-to)	57-62
Number of pages	6
Journal	Lung Cancer
Volume	78
Issue number	1
DOIs	https://doi.org/10.1016/j.lungcan.2012.06.003
State	Published - Oct 2012

Bibliographical note

Funding Information:
The authors acknowledge the efforts of Noelle Gasco of Eli Lilly and Company for editorial assistance and Sarita Dubey, MD, and other co-investigators for patient accrual and treatment on this trial. The study described in this publication was supported by Eli Lilly and Company and in part by the Stanford NIH/NCRR CTSA award number UL1 RR025744.

Funding Information:
T. Jahan has received grant support from Eli Lilly and Company. C. Clément-Duchêne, Y. Krupitskaya, R.B. Natale, R. Osarogiagbon, R.E. Sanborn, and E. Bernstein declare no relevant financial conflicts of interest. A.Z. Dudek participated in advisory boards for Eli Lilly and Company 3 years ago. J.E. Latz and P. Shi are employees of Eli Lilly and Company with ownership of Lilly stock. H.A. Wakelee has received grant support from Eli Lilly and Company and Genentech for clinical trial work.

Keywords

Enzastaurin
Erlotinib
NSCLC

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.lungcan.2012.06.003

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Clément-Duchêne, C., Natale, R. B., Jahan, T., Krupitskaya, Y., Osarogiagbon, R., Sanborn, R. E., Bernstein, E. D., Dudek, A. Z., Latz, J. E., Shi, P., & Wakelee, H. A. (2012). A phase II study of enzastaurin in combination with erlotinib in patients with previously treated advanced non-small cell lung cancer. Lung Cancer, 78(1), 57-62. https://doi.org/10.1016/j.lungcan.2012.06.003

Clément-Duchêne, C, Natale, RB, Jahan, T, Krupitskaya, Y, Osarogiagbon, R, Sanborn, RE, Bernstein, ED, Dudek, AZ, Latz, JE, Shi, P & Wakelee, HA 2012, 'A phase II study of enzastaurin in combination with erlotinib in patients with previously treated advanced non-small cell lung cancer', Lung Cancer, vol. 78, no. 1, pp. 57-62. https://doi.org/10.1016/j.lungcan.2012.06.003

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title = "A phase II study of enzastaurin in combination with erlotinib in patients with previously treated advanced non-small cell lung cancer",

abstract = "Introduction: Regardless of epidermal growth factor receptor (EGFR) mutation status, erlotinib improves survival for patients with advanced non-small cell lung cancer (NSCLC) after one or more chemotherapy regimens. Enzastaurin is an oral serine/threonine kinase inhibitor. This phase II study was designed to evaluate the efficacy and safety of erlotinib and enzastaurin in NSCLC, a combination with promise to overcome EGFR resistance based on preclinical models. Methods: Eligible patients with advanced NSCLC (IIIB or IV) who had failed one or two prior systemic treatment regimen(s) were enrolled and received erlotinib 150. mg/day and enzastaurin 500. mg/day (after a 1125-mg loading dose on day 1, cycle 1), both orally in 28-day cycles. The primary endpoint was progression-free survival (PFS). Results: From January 2008 to July 2009, 49 patients were enrolled: 29 (59%) men and 20 (41%) women; 8 (16%) were non-smokers. The median PFS was 1.7. months (one-sided 90% CI: 1.5-NA) and median overall survival (OS) was 8.3. months (95% CI: 5.3-14.3). Five patients had partial response, for an overall response rate of 10.2%; the disease control rate was 30.6% (responders. +. 10 patients with stable disease). Grade 3-4 drug-related adverse events in ≥5% of patients were diarrhea, acne, and nausea. One possibly drug-related death due to interstitial lung disease occurred during the study. Conclusions: In previously treated, unselected, advanced NSCLC patients, the addition of enzastaurin to erlotinib did not improve PFS, response, or OS compared with historical data of single-agent erlotinib, but was well tolerated.",

keywords = "Enzastaurin, Erlotinib, NSCLC",

author = "Christelle Cl{\'e}ment-Duch{\^e}ne and Natale, {Ronald B.} and Thierry Jahan and Yelena Krupitskaya and Raymond Osarogiagbon and Sanborn, {Rachel E.} and Bernstein, {Eric D.} and Dudek, {Arkadiusz Z.} and Latz, {Jane E.} and Peipei Shi and Wakelee, {Heather A.}",

note = "Funding Information: The authors acknowledge the efforts of Noelle Gasco of Eli Lilly and Company for editorial assistance and Sarita Dubey, MD, and other co-investigators for patient accrual and treatment on this trial. The study described in this publication was supported by Eli Lilly and Company and in part by the Stanford NIH/NCRR CTSA award number UL1 RR025744. Funding Information: T. Jahan has received grant support from Eli Lilly and Company. C. Cl{\'e}ment-Duch{\^e}ne, Y. Krupitskaya, R.B. Natale, R. Osarogiagbon, R.E. Sanborn, and E. Bernstein declare no relevant financial conflicts of interest. A.Z. Dudek participated in advisory boards for Eli Lilly and Company 3 years ago. J.E. Latz and P. Shi are employees of Eli Lilly and Company with ownership of Lilly stock. H.A. Wakelee has received grant support from Eli Lilly and Company and Genentech for clinical trial work. ",

year = "2012",

month = oct,

doi = "10.1016/j.lungcan.2012.06.003",

language = "English (US)",

volume = "78",

pages = "57--62",

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T1 - A phase II study of enzastaurin in combination with erlotinib in patients with previously treated advanced non-small cell lung cancer

AU - Clément-Duchêne, Christelle

AU - Natale, Ronald B.

AU - Jahan, Thierry

AU - Krupitskaya, Yelena

AU - Osarogiagbon, Raymond

AU - Sanborn, Rachel E.

AU - Bernstein, Eric D.

AU - Dudek, Arkadiusz Z.

AU - Latz, Jane E.

AU - Shi, Peipei

AU - Wakelee, Heather A.

N1 - Funding Information: The authors acknowledge the efforts of Noelle Gasco of Eli Lilly and Company for editorial assistance and Sarita Dubey, MD, and other co-investigators for patient accrual and treatment on this trial. The study described in this publication was supported by Eli Lilly and Company and in part by the Stanford NIH/NCRR CTSA award number UL1 RR025744. Funding Information: T. Jahan has received grant support from Eli Lilly and Company. C. Clément-Duchêne, Y. Krupitskaya, R.B. Natale, R. Osarogiagbon, R.E. Sanborn, and E. Bernstein declare no relevant financial conflicts of interest. A.Z. Dudek participated in advisory boards for Eli Lilly and Company 3 years ago. J.E. Latz and P. Shi are employees of Eli Lilly and Company with ownership of Lilly stock. H.A. Wakelee has received grant support from Eli Lilly and Company and Genentech for clinical trial work.

PY - 2012/10

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N2 - Introduction: Regardless of epidermal growth factor receptor (EGFR) mutation status, erlotinib improves survival for patients with advanced non-small cell lung cancer (NSCLC) after one or more chemotherapy regimens. Enzastaurin is an oral serine/threonine kinase inhibitor. This phase II study was designed to evaluate the efficacy and safety of erlotinib and enzastaurin in NSCLC, a combination with promise to overcome EGFR resistance based on preclinical models. Methods: Eligible patients with advanced NSCLC (IIIB or IV) who had failed one or two prior systemic treatment regimen(s) were enrolled and received erlotinib 150. mg/day and enzastaurin 500. mg/day (after a 1125-mg loading dose on day 1, cycle 1), both orally in 28-day cycles. The primary endpoint was progression-free survival (PFS). Results: From January 2008 to July 2009, 49 patients were enrolled: 29 (59%) men and 20 (41%) women; 8 (16%) were non-smokers. The median PFS was 1.7. months (one-sided 90% CI: 1.5-NA) and median overall survival (OS) was 8.3. months (95% CI: 5.3-14.3). Five patients had partial response, for an overall response rate of 10.2%; the disease control rate was 30.6% (responders. +. 10 patients with stable disease). Grade 3-4 drug-related adverse events in ≥5% of patients were diarrhea, acne, and nausea. One possibly drug-related death due to interstitial lung disease occurred during the study. Conclusions: In previously treated, unselected, advanced NSCLC patients, the addition of enzastaurin to erlotinib did not improve PFS, response, or OS compared with historical data of single-agent erlotinib, but was well tolerated.

AB - Introduction: Regardless of epidermal growth factor receptor (EGFR) mutation status, erlotinib improves survival for patients with advanced non-small cell lung cancer (NSCLC) after one or more chemotherapy regimens. Enzastaurin is an oral serine/threonine kinase inhibitor. This phase II study was designed to evaluate the efficacy and safety of erlotinib and enzastaurin in NSCLC, a combination with promise to overcome EGFR resistance based on preclinical models. Methods: Eligible patients with advanced NSCLC (IIIB or IV) who had failed one or two prior systemic treatment regimen(s) were enrolled and received erlotinib 150. mg/day and enzastaurin 500. mg/day (after a 1125-mg loading dose on day 1, cycle 1), both orally in 28-day cycles. The primary endpoint was progression-free survival (PFS). Results: From January 2008 to July 2009, 49 patients were enrolled: 29 (59%) men and 20 (41%) women; 8 (16%) were non-smokers. The median PFS was 1.7. months (one-sided 90% CI: 1.5-NA) and median overall survival (OS) was 8.3. months (95% CI: 5.3-14.3). Five patients had partial response, for an overall response rate of 10.2%; the disease control rate was 30.6% (responders. +. 10 patients with stable disease). Grade 3-4 drug-related adverse events in ≥5% of patients were diarrhea, acne, and nausea. One possibly drug-related death due to interstitial lung disease occurred during the study. Conclusions: In previously treated, unselected, advanced NSCLC patients, the addition of enzastaurin to erlotinib did not improve PFS, response, or OS compared with historical data of single-agent erlotinib, but was well tolerated.

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KW - Erlotinib

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A phase II study of enzastaurin in combination with erlotinib in patients with previously treated advanced non-small cell lung cancer

Abstract

Bibliographical note

Keywords

UN SDGs

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