Phase II, double-blinded, randomized study of enzastaurin plus pemetrexed as second-line therapy in patients with advanced non-small cell lung cancer

Alberto Chiappori, Gerold Bepler, Fabrice Barlesi, Jean Charles Soria, Martin Reck, Alessandra Bearz, Fernando Barata, Giorgio Scagliotti, Keunchil Park, Asavari Wagle, Astra M. Liepa, Yan Daniel Zhao, Nadia Chouaki, Neill Iscoe, Joachim Von Pawel

Research output: Contribution to journalArticle

Abstract

Introduction: We examined the efficacy of enzastaurin plus pemetrexed as second-line therapy in patients with advanced (stage IIIA/B or IV) non-small cell lung cancer in a double-blinded, randomized, phase II study. Methods: Patients received pemetrexed 500 mg/m intravenously on day 1 of 21-day cycles (day 8 in cycle 1) plus oral enzastaurin (250 mg two times per day; combination arm) or placebo (pemetrexed arm). Both arms received supplementation with vitamin B12, folic acid, and dexamethasone. An interim analysis was conducted to determine whether efficacy would warrant a phase III study. Results: The interim analysis showed no evidence of improved progression-free survival with enzastaurin. At final analysis (N = 160, 80 in each arm), baseline characteristics were well balanced. There was no significant difference in progression-free survival (3.0 months, p = 0.544) or overall survival (9.6 months in combination arm and 7.4 months in pemetrexed arm, p = 0.171). Drug-related serious adverse events included cerebrovascular accident, palpitations, and renal failure (n = 1, each) in combination arm and neutropenic sepsis, thrombocytopenia, and panniculitis (n = 1, each) in pemetrexed arm. Nonhematologic drug-related grade 3/4 toxicities were similar in both arms. Grade 3/4 hematologic toxicities were higher with the combination, specifically leukopenia (6.3% versus 0%), neutropenia (15.2% versus 5.0%), and thrombocytopenia (8.9% versus 1.3%). Of the 26 deaths reported on-study or within 30 days of discontinuation (10 in combination arm and 16 in pemetrexed arm), none were drug related. Conclusion: The combination regimen of enzastaurin and pemetrexed is well tolerated but does not improve efficacy over pemetrexed and placebo as second-line treatment of unselected patients with advanced non-small cell lung cancer.

Original languageEnglish
Pages (from-to)369-375
Number of pages7
JournalJournal of Thoracic Oncology
Volume5
Issue number3
DOIs
Publication statusPublished - Mar 2010

Keywords

  • Enzastaurin
  • Non-small cell lung cancer
  • Pemetrexed
  • Phase II

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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    Chiappori, A., Bepler, G., Barlesi, F., Soria, J. C., Reck, M., Bearz, A., Barata, F., Scagliotti, G., Park, K., Wagle, A., Liepa, A. M., Zhao, Y. D., Chouaki, N., Iscoe, N., & Von Pawel, J. (2010). Phase II, double-blinded, randomized study of enzastaurin plus pemetrexed as second-line therapy in patients with advanced non-small cell lung cancer. Journal of Thoracic Oncology, 5(3), 369-375. https://doi.org/10.1097/JTO.0b013e3181cee24f