Analysis of prognostic factors in chemo-naïve patients with advanced NSCLC and poor performance status (PS): Cox regression analysis of two phase III trials

Abstract

7113 Background: Two phase III trials in chemo-naïve PS2 patients with advanced NSCLC compared paclitaxel poliglumex (PPX) to either gemcitabine or vinorelbine (STELLAR 4), or PPX/carboplatin to paclitaxel/carboplatin (STELLAR 3). While overall survival (OS) was similar between treatment arms in both studies, individual patient characteristics may be predictive of benefit. Methods: STELLAR 3 and STELLAR 4 enrolled 400 and 381 chemo-naïve PS2 patients, respectively. The impact of pre-defined baseline characteristics on OS was evaluated by univariate and step-wise multivariate Cox regression analysis. Treatment differences between subgroups were also estimated by Cox analysis. Results: Univariate Cox analysis of potential risk factors showed pre-baseline weight loss, extra-thoracic metastasis, and a low lung cancer symptom (LCS) score to be highly significant (p < 0.001). In STELLAR 4, tobacco use was also a highly significant risk factor. Important primary baseline factors predicting survival as determined by multivariate analysis are summarized in the table . Other baseline factors evaluated but not predictive of survival included gender, number of comorbidities, age, and history of tobacco use. Treatment differences between subgroups were not statistically significant; however, a strong trend towards improved survival was observed for women receiving PPX in STELLAR 4 compared to those in the control-arm (HR = 0.65; p = 0.069). In contrast, men had similar survival between treatment arms (HR = 1.08; p = 0.579). Conclusion: In this large PS2 patient population, weight loss, presence of extra-thoracic metastasis, low LCS scores, and high LDH were found to be important clinical determinants of survival. In addition, significant differences in survival based on geographic region in STELLAR 3 highlight the importance of stratification by region. [Table: see text] [Table: see text]

Polymer-drug conjugates: current status and future trends

“…This conjugate has been tested clinically for the treatment of a variety of solid tumors. A recent phase III study in patients with NSCLC highlighted a trend of improved survival in women (26,29). Although statistical significance was not reached, this observation prompted further investigation to understand the reasons for the increased efficacy in women.…”