Bortezomib ± docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC): A phase 2 study

Abstract

7034 Background: Bortezomib (VELCADE, Vc, Millennium Pharmaceuticals), a novel proteasome inhibitor, has demonstrated activity against NSCLC as monotherapy in preclinical and phase 1 studies. At the interim analysis of this randomized, multicenter phase 2 study (J Clin Oncol. 2004;22[suppl 14s]:643s), efficacy criteria for continuing the study were met, and toxicity was manageable. Thus, enrollment continued to the full accrual goal, targeted at 155 patients (pts). Methods: Major eligibility criteria: age ≥ 18 y, stage IIIB or IV NSCLC, Karnofsky performance score (KPS) ≥ 70%, and 1 prior chemotherapy regimen. Arm A received Vc 1.5 mg/m2 IV bolus on d 1, 4, 8, and 11 q 21d. Arm B received dexamethasone premedication, docetaxel (TAXOTERE, Tax) 75 mg/m2 IV over 1 hr on d 1 and Vc 1.3 mg/m2 (1 hr after Tax) on d 1, 4, 8, and 11 q 21 d. The primary objective was to assess response to Vc ± Tax. Secondary objectives were safety, tolerability, survival, pharmacokinetics, pharmacodynamics, and pharmacogenomics. Results: 155 pts were enrolled, and data are currently available for the first 62 pts. Arm A had 30 pts, median age 63 y (range, 40–78), 83% prior paclitaxel, 80% KPS ≥ 80%. Arm B had 32 pts, median age 65 y (range, 20–82), 66% prior paclitaxel, 88% KPS ≥ 80%. Arm A demonstrated a partial response (PR) rate by RECIST of 10.0% (3/30). In arm B, the PR rate was 15.6% (5/32), and toxicities were manageable. Median time to progression was 42.5 d in arm A and 86 d in arm B; median duration of response was 299 d (9.8 mo) in arm A and has not yet been reached in arm B, but it is at least 9.8+ mo after a median follow-up of 8.0 mo (n = 5). The median duration of disease stabilization (complete response, PR, or stable disease) was 126 d (4.1 mo) in arm A (n = 8) and 160 d (5.3 mo) in arm B (n = 19). Treatment was well tolerated on both arms. The most common ≥ grade 3 events were dehydration, nausea, and vomiting in arm A, and neutropenia, fatigue, and diarrhea in arm B. Conclusion: Vc demonstrates encouraging activity in pts with NSCLC, both as a single agent and in combination with Tax, and toxicities are manageable. The final analysis is ongoing; updated results for all 158 pts will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly, EMD, Genentech, Millennium, Taiho Amgen, AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly, Genentech, GlaxoSmithKline, Lilly Oncology, Merck, Pfizer, Taiho AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly, Ligand, Lilly Oncology, Millennium, Pfizer AstraZeneca Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly