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

Abstract

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. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .