Preliminary results of a randomized phase II trial of pemetrexed (P) + carboplatin (Cb) ± enzastaurin (ENZ) versus docetaxel (D) + Cb as first-line treatment of patients with stage IIIB/IV non-small cell lung cancer (NSCLC).

8061 Background: ENZ is a selective, oral serine/threonine kinase inhibitor. The combination of PCb has shown clinical activity in two phase 2 trials of advanced NSCLC. A phase 3 trial among pts with stage IIIB/IV NSCLC showed that P + cisplatin (C) provides similar efficacy with better tolerability than gemcitabine + C (Scagliotti, IASLC 2007; PRS-03). In the TAX 326 trial, DCb was associated with a median survival of 11.3 mos vs. 10.1 mos for vinorelbine + C (P=.04). This open-label three-arm trial was designed to assess PCb ± ENZ versus a control arm of DCb.,Pts with Stage IIIB (with pleural effusion) or IV NSCLC, ECOG PS of 0 or 1, and no prior systemic therapy were enrolled. Pts were equally randomized to one of three arms: (A) P 500 mg/m and Cb AUC 6 every 3 wks X 6 cycles with ENZ given orally as a loading dose of 1200 mg or 1125 mg followed by 500 mg daily until disease progression; (B) The same regimen of PCb without ENZ; or (C) D 75 mg/m and Cb AUC 6 every 3 wks X 6 cycles. Pts receiving P were also administered folic acid, vitamin B12 and steroid prophylaxis. Pts on D also received steroid prophylaxis.,See table .,PCb+ENZ, PCb, and DCb appear to be well tolerated in advanced or metastatic NSCLC. In this trial, first-line treatment with PCb ± ENZ (compared with DCb) was associated with a greater incidence of grade 3/4 anemia or thrombocytopenia but less grade 4 neutropenia and grade 2 alopecia. Updated results for all pateints in the study will be available at the time of the meeting. [Table: see text] [Table: see text].