TY - JOUR
T1 - Phase II, double-blinded, randomized study of enzastaurin plus pemetrexed as second-line therapy in patients with advanced non-small cell lung cancer
AU - Chiappori, Alberto
AU - Bepler, Gerold
AU - Barlesi, Fabrice
AU - Soria, Jean Charles
AU - Reck, Martin
AU - Bearz, Alessandra
AU - Barata, Fernando
AU - Scagliotti, Giorgio
AU - Park, Keunchil
AU - Wagle, Asavari
AU - Liepa, Astra M.
AU - Zhao, Yan Daniel
AU - Chouaki, Nadia
AU - Iscoe, Neill
AU - Von Pawel, Joachim
N1 - Funding Information:
Supported by Eli Lilly and Company.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - 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.
AB - 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.
KW - Enzastaurin
KW - Non-small cell lung cancer
KW - Pemetrexed
KW - Phase II
UR - http://www.scopus.com/inward/record.url?scp=77649320148&partnerID=8YFLogxK
U2 - 10.1097/JTO.0b013e3181cee24f
DO - 10.1097/JTO.0b013e3181cee24f
M3 - Article
AN - SCOPUS:77649320148
SN - 1556-0864
VL - 5
SP - 369
EP - 375
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 3
ER -