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)
Authors: D. M. Kocs, R. N. Raju, M. A. Socinski, T. E. Stinchcombe, S. R. Rousey, D. Barrera, Y. Wang, J. Bromund, J. Treat, C. K. Obasaju
Journal: Journal of Clinical Oncology (2008)

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. Methods: 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/m2 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/m2 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. Results: See table. Conclusions: 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. Characteristics/Results PCb+ENZ (Arm A) PCb (Arm B) DCb (Arm C) No. of available pts 53 55 51 Median age, yrs 67 67 65 Male gender 55% 53% 53% Brain metastasis 9% 11% 8% ECOG Performance Status – – – PS 0 47% 44% 41% PS 1 45% 46% 53% Missing 8% 11% 6% Mean no. of cycles of PCb or DCb 3.7 4.1 3.2 Dose reductions or delays – – – P or D 33% 29% 17% Cb 35% 29% 15% Mean relative dose intensity – – – P or D 89% 91% 93% Cb 85% 87% 90% Compliance with ENZ 84% – – No. pts assessed for safety 42 48 46 Neutropenia, Grade 3/4 24%/12% 23%/6% 20%/20% Anemia, Grade 3/4 7%/2% 17%/0% 0%/0% Thrombocytopenia, Grade 3/4 14%/12% 10%/8% 2%/0% Febrile neutropenia Grade 3/4 0%/0% 2%/0% 2%/2%< Fatigue, Grade 3/4 2%/0% 0%/0% 7%/0% Diarrhea, Grade 3/4 5%/0% 0%/0% 7%/0% Pain, Grade 3/4 0%/0% 4%/0% 9%/0% Alopecia, Grade 2 0% 6% 13% Elevated ALT, Grade 3/4 2%/0% 0%/0% 0%/0% Pulmonary embolus, Grade 3/4 0%/0% 0%/4% 2%/4% Dyspnea, Grade 3/4 0%/0% 2%/0% 4%/2% Dizziness, Grade 3/4 0%/0% 2%/0% 2%/0% Dehydration, Grade 3/4 2%/0% 0%/0% 9%/0% Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company