Brief report: a phase II "window-of-opportunity" frontline study of the MTOR inhibitor, temsirolimus given as a single agent in patients with advanced NSCLC, an NCCTG study - PubMed (original) (raw)

Clinical Trial

doi: 10.1097/JTO.0b013e31824de0d6.

Julian R Molina, Sumithra J Mandrekar, Katie Allen-Ziegler, Kendrith M Rowland, Nicholas F Reuter, Ronnie F Luyun, Grace K Dy, Randolph S Marks, Steven E Schild, James R Jett, Alex A Adjei

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Clinical Trial

Brief report: a phase II "window-of-opportunity" frontline study of the MTOR inhibitor, temsirolimus given as a single agent in patients with advanced NSCLC, an NCCTG study

Thanyanan Reungwetwattana et al. J Thorac Oncol. 2012 May.

Abstract

Background: In an effort to evaluate the single agent activity of temsirolimus in previously untreated non-small-cell lung cancer, the North Central Cancer Treatment Group undertook a frontline "window-of-opportunity" study.

Methods: Patients received 25 mg of temsirolimus administered intravenously as a weekly 30 minute infusion, on a 4-week cycle. Based on a two-stage Fleming design, the treatment would be promising if at least four of the first 25 evaluable patients in stage I or at least six of the 50 evaluable patients at the end of stage II have a confirmed response. Fresh tumor biopsies were obtained to evaluate predictive markers of temsirolimus activity.

Results: A total of 55 patients were enrolled with 52 patients being evaluable. The median age was 64 years. Adverse events (grade 3/4) occurring in 33 patients included dyspnea (12%), fatigue (10%), hyperglycemia (8%), hypoxia (8%), nausea (8%), and rash/desquamation (6%). The clinical benefit rate was 35% with four patients achieving a confirmed partial response and 14 patients with stable disease for 8 weeks or more. The 24-week progression-free survival rate was 25%. Median progression-free survival and overall survival were 2.3 and 6.6 months, respectively. Expression of p70s6 kinase, phospho-p70s6 kinase, Akt, phospho-Akt, and phosphatase and tensin homolog mutation did not correlate with clinical outcome.

Conclusions: Temsirolimus given as a single agent in frontline therapy in patients with non-small-cell lung cancer was tolerable and demonstrated clinical benefit but did not meet the primary objective in this study. Patient selection will be needed to enhance the efficacy.

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Conflict of interest statement

Disclosure: The authors declare no conflict of interest.

Figures

FIGURE 1

FIGURE 1

Computed tomography chest showed partial response during the treatment of one of the participating patients.

FIGURE 2

FIGURE 2

Kaplan-Meier survival curve. CI, confidence interval.

FIGURE 3

FIGURE 3

Immunohistochemistry staining of p70s6kinase phosphorylation in pretreatment tumor samples.

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