TY - JOUR
T1 - Class III β-tubulin in advanced NSCLC of adenocarcinoma subtype predicts superior outcome in a randomized trial
AU - Vilmar, Adam Christian
AU - Santoni-Rugiu, Eric
AU - Sørensen, Jens Benn
N1 - ©2011 AACR.
PY - 2011/8/1
Y1 - 2011/8/1
N2 - Purpose: Platinum-based doublets are the cornerstone of treatment in advanced non - small-cell lung cancer (NSCLC) and often include vinorelbine or taxanes. A predictive biomarker is greatly needed to select chemotherapy- sensitive patients for these microtubule-interfering agents. Class III β-tubulin (TUBB3) has been shown of value in NSCLC, but evidence is not uniform. Accordingly, we explored the predictive role of TUBB3 in advanced NSCLC. Experimental Design: Four hundred forty-three patients with advanced NSCLC were enrolled in a phase III trial and randomized to vinorelbine- or paclitaxel-containing chemotherapy. Immunohistochemical evaluation of TUBB3 status was mainly done on bioptic material and correlated to response rates, progression-free survival (PFS), overall survival (OS), quality of life (QOL), and toxicity. Results: Two hundred sixty-one (58.9%) patients had representative tissue samples for TUBB3 evaluation. Patients with TUBB3-negative adenocarcinomas had a significantly prolonged PFS and OS when compared with the opposite subgroup (7.87 vs. 6.83 months, P = 0.035 and 14.17 vs. 11.17 months, P = 0.018, respectively). Multivariate analyses revealed an HR of 1.55 (95% CI, 1.04-2.31, P = 0.032) for TUBB3-positive adenocarcinoma patients. TUBB3-negative adenocarcinoma patients showed a mean QOL decline of -18.25 points (95% CI, -4.28 to -32.22, P = 0.013) as compared with -3.86 (95% CI, -7.0 to 15.52, P = 0.5). Conclusion: TUBB3 was of predictive value in adenocarcinoma patients in the largest, randomized advanced NSCLC population published to date. It may be clinically useful in conjunction with other biomarkers, but QOL information should be recorded during validation, as prophylactic intervention may be needed in specific subgroups at risk of toxicity.
AB - Purpose: Platinum-based doublets are the cornerstone of treatment in advanced non - small-cell lung cancer (NSCLC) and often include vinorelbine or taxanes. A predictive biomarker is greatly needed to select chemotherapy- sensitive patients for these microtubule-interfering agents. Class III β-tubulin (TUBB3) has been shown of value in NSCLC, but evidence is not uniform. Accordingly, we explored the predictive role of TUBB3 in advanced NSCLC. Experimental Design: Four hundred forty-three patients with advanced NSCLC were enrolled in a phase III trial and randomized to vinorelbine- or paclitaxel-containing chemotherapy. Immunohistochemical evaluation of TUBB3 status was mainly done on bioptic material and correlated to response rates, progression-free survival (PFS), overall survival (OS), quality of life (QOL), and toxicity. Results: Two hundred sixty-one (58.9%) patients had representative tissue samples for TUBB3 evaluation. Patients with TUBB3-negative adenocarcinomas had a significantly prolonged PFS and OS when compared with the opposite subgroup (7.87 vs. 6.83 months, P = 0.035 and 14.17 vs. 11.17 months, P = 0.018, respectively). Multivariate analyses revealed an HR of 1.55 (95% CI, 1.04-2.31, P = 0.032) for TUBB3-positive adenocarcinoma patients. TUBB3-negative adenocarcinoma patients showed a mean QOL decline of -18.25 points (95% CI, -4.28 to -32.22, P = 0.013) as compared with -3.86 (95% CI, -7.0 to 15.52, P = 0.5). Conclusion: TUBB3 was of predictive value in adenocarcinoma patients in the largest, randomized advanced NSCLC population published to date. It may be clinically useful in conjunction with other biomarkers, but QOL information should be recorded during validation, as prophylactic intervention may be needed in specific subgroups at risk of toxicity.
U2 - 10.1158/1078-0432.ccr-11-0658
DO - 10.1158/1078-0432.ccr-11-0658
M3 - Journal article
SN - 1078-0432
VL - 17
SP - 5205
EP - 5214
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 15
ER -
