Randomized Phase II Study of Ixabepilone or Paclitaxel Plus Carboplatin in Patients With Non-Small-Cell Lung Cancer Prospectively Stratified by Beta-3 Tubulin Status

Purpose Retrospective studies have reported that tumor expression of the beta-3 tubulin (beta 3T) isoform is an unfavorable prognostic factor in non-small-cell lung cancer (NSCLC) treated with tubulin-inhibiting chemotherapy. Ixabepilone is a tubulin-inhibiting agent with low susceptibility to multiple resistance mechanisms including beta 3T isoform expression in several tumor models. This randomized phase II study evaluated ixabepilone-based chemotherapy in stage IIIb/IV NSCLC, compared with paclitaxel-based chemotherapy. Tumor specimens were prospectively evaluated for beta 3T expression. Patients and Methods Patients were stratified by beta 3T status (positive v negative) and randomly assigned at a ratio of 1:1 to receive ixabepilone (32 mg/m(2)) and carboplatin (area under concentration-time curve [AUC], 6) or paclitaxel (200 mg/m(2)) and carboplatin (AUC, 6) for up to six cycles. The primary end point was progression-free survival (PFS) in the beta 3T-positive subgroup. Results Ninety-five patients (beta 3T positive, 52; beta 3T negative, 43) received ixabepilone plus carboplatin; 96 patients (beta 3T positive, 49; beta 3T negative, 47) received paclitaxel plus carboplatin. No significant differences in median PFS were observed between arms for either subgroup (beta 3T positive, 4.3 months in both arms; beta 3T negative, 5.8 v 5.3 months). Ixabepilone did not significantly improve overall survival (OS) for the beta 3T-positive subset or the overall population. Adverse events were similar between the two arms and comparable with those in previous studies. Conclusion There was no predictive value of beta 3T in differentiating clinical activity of ixabepilone- or paclitaxel-containing regimens. Ixabepilone did not improve PFS or OS in patients with beta 3T-positive tumors. beta 3T-positive patients had worse PFS relative to beta 3T-negative patients, regardless of treatment; hence, beta 3T expression seems to be a negative prognostic factor, but not a predictive factor, in advanced NSCLC treated with either ixabepilone or paclitaxel platinum-based doublets. (c) 2013 by American Society of Clinical Oncology