Department of Oncology 5073, Finsen Centre, and Department of Pathology 5442, Diagnostic Center, National University Hospital, Copenhagen, Denmark.
Clin Cancer Res. 2011 Aug 1;17(15):5205-14. doi: 10.1158/1078-0432.CCR-11-0658. Epub 2011 Jun 20.
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.
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.
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).
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.
铂类双联方案是晚期非小细胞肺癌（NSCLC）治疗的基石，其中常包含长春瑞滨或紫杉类药物。为了选择对这些微管干扰剂敏感的化疗患者，我们迫切需要一种预测性生物标志物。III 类 β-微管蛋白（TUBB3）在 NSCLC 中已有价值的证据，但并不一致。因此，我们探索了 TUBB3 在晚期 NSCLC 中的预测作用。
443 例晚期 NSCLC 患者入组一项 III 期临床试验，随机分配至长春瑞滨或紫杉醇化疗组。TUBB3 状态的免疫组织化学评估主要在活检标本上进行，并与缓解率、无进展生存期（PFS）、总生存期（OS）、生活质量（QOL）和毒性相关。
261 例（58.9%）患者有代表性的 TUBB3 评估组织样本。与相反亚组相比，TUBB3 阴性腺癌患者的 PFS 和 OS 显著延长（7.87 与 6.83 个月，P=0.035 和 14.17 与 11.17 个月，P=0.018）。多变量分析显示 TUBB3 阳性腺癌患者的 HR 为 1.55（95%CI，1.04-2.31，P=0.032）。TUBB3 阴性腺癌患者的 QOL 平均下降 18.25 分（95%CI，-4.28 至-32.22，P=0.013），而 TUBB3 阳性患者下降 3.86 分（95%CI，-7.0 至 15.52，P=0.5）。
TUBB3 在迄今为止发表的最大随机晚期 NSCLC 人群中对腺癌患者具有预测价值。它可能与其他生物标志物一起具有临床应用价值，但在验证过程中应记录 QOL 信息，因为在有潜在毒性风险的特定亚组中可能需要预防性干预。
