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Effect of gender on outcome in two randomized phase III trials of paclitaxel poliglumex (PPX) in chemonaïve pts with advanced NSCLC and poor performance status (PS2)

2006; Lippincott Williams & Wilkins; Volume: 24; Issue: 18_suppl Linguagem: Inglês

10.1200/jco.2006.24.18_suppl.7039

1527-7755

Helen J. Ross, Philip Bonomi, Corey J. Langer, Mary O’Brien, Kenneth J. O’Byrne, Luís Paz-Ares, Alan Sandler, Mark A. Socinski, F. B. Oldham, Jack W. Singer,

Cancer Treatment and Pharmacology

7039 Background: Women with NSCLC are younger and are more likely to be non-smokers than the overall NSCLC population. Estrogen seems to contribute to these differences in lung cancer biology, but its effect on treatment efficacy has not been well described. Methods: Two phase III trials in chemo-naïve PS2 patients with advanced NSCLC compared PPX to either gemcitabine or vinorelbine (STELLAR 4), or PPX/carboplatin to paclitaxel/carboplatin (STELLAR 3). Eligibility criteria were identical and pts were stratified for gender and age. Analysis of overall survival (OS), the primary study endpoint, showed similar survival between treatment arms. A trend to improvement with PPX for females but not males in both studies prompted an exploratory combined analysis of the 198 women in STELLAR 3 (93/400 pts) and STELLAR 4 (105/381 pts) using univariate and multivariate Cox regression analysis of OS. Results: Combined log-rank analysis of STELLAR 3 and 4 shows improved OS for females receiving PPX vs control (9.5 mo vs 7.8 mo; HR=0.70; p=0.03) and no difference in males (7.3 mo vs 6.9 mo; HR=1.06; p=0.53). Cox multivariate analysis identified treatment with PPX (HR=0.64; p=0.019), smoking (HR=1.50; p=0.037), and presence of extra-thoracic metastases (HR=1.76; p=0.003) as independent prognostic factors in these women. In the combined analysis, median survival advantage for PPX-treated pts was greater in women <55 years old (10.0 vs 5.2 mo, p=0.038) compared to women 55 or older (8.9 vs 8.6 mo, p=0.134). Pretreatment estrogen levels were available for 86 pts in STELLAR 3; pts with estrogen >30 pg/dl had a significant survival benefit when receiving PPX compared to paclitaxel (10.2 vs 5.5 mo; p=0.039). Conclusions: While the efficacy of PPX is comparable to other treatment options in NSCLC, PPX may be more effective female pts, particularly premenopausal women, compared to females in the control arms. Preclinical data suggest that estrogen enhances PPX distribution to lung tissue and upregulates the rate-limiting metabolic enzyme cathepsin B in NSCLC. To prospectively test the effect of estrogen on OS, a phase III trial (PIONEER) has been initiated to compare PPX to paclitaxel in chemo-naïve PS2 females with NSCLC. [Table: see text]