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Oral Oncol. 2015 Apr;51(4):383-8. doi: 10.1016/j.oraloncology.2014.12.013. Epub 2015 Jan 13.

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 head and neck squamous cell cancer.

Author information

1
University of Colorado School of Medicine, Aurora, CO, United States. Electronic address: antonio.jimeno@ucdenver.edu.
2
University of Pittsburgh Cancer Institute, Pittsburgh, PA, United States.
3
New York Hematology, New York, NY, United States.
4
Washington University, St. Louis, MO, United States.
5
Compass Oncology, Tualatin, OR, United States; US Oncology Research, The Woodlands, TX, United States.
6
CHUS Hôpital Fleurimont, Quebec, Canada.
7
University of Colorado School of Medicine, Aurora, CO, United States; Denver Veterans Affairs Medical Center, Denver, CO, United States.
8
Virginia Cancer Specialists, Fairfax, VA, United States; US Oncology Research, The Woodlands, TX, United States.
9
Beth Israel Hospital, St. Luke's Hospital, Mount Sinai Health System, New York, NY, United States.
10
New York University, New York, NY, United States.
11
Oncothyreon Inc., Seattle, WA, United States.
12
Johns Hopkins University, Baltimore, MD, United States.
13
Medical University of South Carolina, Charleston, SC, United States.

Abstract

INTRODUCTION:

The phosphotidylinositol-3 kinase (PI3K)/serine-threonine kinase (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is frequently altered in head and neck squamous cell cancer (HNSCC). PX-866 is an oral, irreversible, pan-isoform inhibitor of PI3K. 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 HNSCC.

METHODS:

Patients with locally advanced, recurrent or metastatic HNSCC who had received at least one and no more than two prior systemic treatment regimens were randomized (1:1) to a combination of docetaxel (75mg/m(2) IV every 21days) with or without PX-866 (8mg PO daily; Arms A and B, respectively). The primary endpoint was progression free survival (PFS). Secondary endpoints included objective response rate (RR), overall survival (OS), toxicity, and correlation of biomarker analyses with efficacy outcomes.

RESULTS:

85 patients were enrolled. There was a non-significant improvement in response rate in the combination arm (14% vs. 5%; P=0.13). Median PFS was 92days in Arm A and 82days in Arm B (P=0.42). There was no difference in OS between the two arms (263 vs. 195days; P=0.62). Grade 3 or higher adverse events were infrequent, but more common in the combination arm with respect to diarrhea (17% vs. 2%), nausea (7% vs. 0%), and febrile neutropenia (21% vs. 5%); grade 3 or higher anemia was more frequent in arm B (7% vs. 27%). PIK3CA mutations or PTEN loss were infrequently observed.

CONCLUSION:

The addition of PX-866 to docetaxel did not improve PFS, RR, or OS in patients with advanced, refractory HNSCC without molecular pre-selection.

KEYWORDS:

Docetaxel; Head and neck squamous cell cancer; PI3K; PIK3CA

[Indexed for MEDLINE]
Free PMC Article

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