Randomized, double blind, multicenter, phase II study of pemetrexed (PEM), carboplatin (CARBO), bevacizumab (BEV) with enzastaurin (ENZ) or placebo (PBO) in chemotherapy-naive patients with stage IIIB/IV non-small cell lung cancer (NSCLC): Hoosier Oncology Group (HOG) LUN06–116
Authors: Casey E. M. , Harb W. , Bradford D. , Bufill J. , Nattam S. , Patel J. , Fisher W. , Latz J. E. , Wu J. , Hanna N. 
Published: August 2020

8035^

Background: Pre-clinical data suggests that ENZ and BEV may have complementary effects in inhibiting angiogenesis. This study compared ENZ vs PBO in combination with PEM+CARBO+ BEV. Methods: Pts ≥18 years of age, non-squamous NSCLC, no prior systemic therapy, disease measurable by RECIST, and ECOG PS 0–1 were randomized. Pts received either PBO or 500 mg ENZ daily after loading dose of 375 mg orally, TID, on day 1, cycle 1. Starting on day 8, cycle 1, patients received PEM 500mg/m2, CARBO AUC 6 and BEV 15mg/kg, intravenously, every 21 days. After 4 cycles, pts continued on BEV+ENZ or BEV+PBO. Pts were stratified by ECOG status, disease stage and site with a planned sample size of 90 pts. Primary end point was progression-free survival (PFS). Secondary end points included objective response rate (ORR) and toxicity. Results: Study was terminated after a planned interim analysis for safety and efficacy. From October 2007 to July 2008, 40 pts were enrolled: 20 in each arm. Median age was 60.5 years (range: 44 to 78); M 52.5%, F 47.5%; ECOG PS 0/1 52.5% and 47.5%; stage IIIB/IV 15% and 85%. Baseline characteristics were well matched. The PEM+CARBO+BEV+ENZ arm received a median of 3 cycles of therapy and the PEM+CARBO+BEV+PBO arm 4 cycles. Median PFS was 4.3 mo and 4.2 mo for ENZ and PBO, respectively (unadjusted HR: 0.94, 95% CI [0.39, 2.33]). ORR for ENZ and PBO was 20% and 25%, respectively. Overall, grade 3/4 toxicities were similar in both arms. One patient in ENZ arm experienced a grade 3/4 hemorrhage (vs. none in the PBO arm). Two patients experienced a GI perforation (1 on each arm): 1 resulted in death on the PBO arm. Both patients had a history of diverticulosis. Conclusions: Based upon the results of this interim efficacy analysis, addition of ENZ to PEM+CARBO+BEV will not significantly prolong PFS in patients with stage IIIB/IV NSCLC. This combination does not warrant further study in NSCLC.

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