Ugh. Kirkman didn't have the courage to deliver on his promise of describing 866 results in PRs, and now we know why.....
J Thorac Oncol. 2014 Jul;9(7):1031-1035.
A Randomized, Phase 2 Trial of Docetaxel with or without PX-866, an Irreversible Oral Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Relapsed or Metastatic Non-Small-Cell Lung Cancer.
Levy B1, Spira A, Becker D, Evans T, Schnadig I, Camidge DR, Bauman JE, Hausman D, Walker L, Nemunaitis J, Rudin CM, Halmos B, Bowles DW.
1*Beth Israel Hospital, St. Luke's Hospital, Mount Sinai Health System, New York, New York; †Virginia Cancer Specialists, Fairfax, Virginia; ‡US Oncology Research, The Woodlands, Texas; §Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania; ?Northwest Cancer Specialists, Portland, Oregon; ¶Division of Medical Oncology, University of Colorado School of Medicine, Aurora, Colorado; #University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; **Oncothyreon Inc., Seattle, Washington; ††Mary Crowley Cancer Research Centers, Dallas, Texas; ‡‡Johns Hopkins University, Baltimore, Maryland; Memorial Sloan Kettering Cancer Center, New York, New York; §§New York-Presbyterian Hospital, Columbia University Medical Center, New York, New York; and ??Section of Hematology/Oncology, Denver Veterans Affairs Medical Center, Denver, Colorado.
INTRODUCTION::
The phosphotidylinositol-3 kinase/serine-threonine kinase (AKT)/mammalian target of rapamycin signaling pathway is frequently altered in non-small-cell lung cancer (NSCLC). PX-866 is an oral, irreversible, pan-isoform inhibitor of phosphotidylinositol-3 kinase. Preclinical models revealed synergy with docetaxel and a phase 1 trial demonstrated tolerability of this combination. This randomized phase 2 study evaluated PX-866 combined with docetaxel in patients with advanced, refractory NSCLC.
METHODS::
Patients with locally advanced, recurrent, or metastatic NSCLC who had received at least one and no more than two prior systemic treatment regimens were randomized (1:1) to a combination of docetaxel (75 mg/m intravenous every 21 days) with or without PX-866 (8 mg orally daily; arms A and B, respectively). The primary end point was progression-free survival (PFS). Secondary end points included objective response rate, overall survival (OS), toxicity, and correlation of biomarker analyses with efficacy outcomes.
RESULTS::
A total of 95 patients were enrolled. Median PFS was 2 months in arm A and 2.9 months in arm B (p = 0.65). Objective response rates were 6% and 0% in arms A and B, respectively (p = 0.4). There was no difference in OS between the two arms (7.0 versus 9.2 months; p = 0.9). Grade 3 or higher adverse events were infrequent, but more common in the combination arm with respect to diarrhea (7% versus 2%), nausea (4% versus 0%), and vomiting (7% versus 0%). PIK3CA mutations or PTEN loss were infrequently observed.
CONCLUSION::
The addition of PX-866 to docetaxel did not improve PFS, response rate, or OS in patients with advanced, refractory NSCLC without molecular preselection. |
