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. Issue 4 (April 2015)

• Record Type: Journal Article
• Authors: Jimeno, Antonio; Bauman, Julie E.; Weissman, Charles; Adkins, Douglas; Schnadig, Ian; Beauregard, Patrice; Bowles, Daniel W.; Spira, Alexander; Levy, Benjamin; Seetharamu, Nagashree; Hausman, Diana; Walker, Luke; Rudin, Charles M.; Shirai, Keisuke
• Is Part Of: Oral oncology. Volume 51:Issue 4(2015:Apr.)
• Page Start: 383
• Page End: 388
• Publication Date: 2015-04
• Subjects: Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2014.12.013
• Languages: English
• ISSNs: 1368-8375

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title id="st090">Summary</title> <sec> <title id="st095">Introduction</title> <p id="sp0005">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.</p> </sec> <sec> <title id="st100">Methods</title> <p id="sp0010">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 (75 mg/m<sup>2</sup> IV every 21 days) with or without PX-866 (8 mg 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.</p> </sec> <sec> <title id="st105">Results</title> <p id="sp0015">85 patients were enrolled. There was a non-significant improvement in response rate in the combination arm (14% vs. 5%; <italic>P</italic> = 0.13). Median PFS was 92 days in Arm A and 82 days in Arm B (<italic>P</italic> = 0.42). There was no difference in OS between the two arms (263 vs. 195 days; <italic>P</italic> = 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%). <italic>PIK3CA</italic> mutations or <italic>PTEN</italic> loss were infrequently observed.</p> </sec> <sec> <title id="st110">Conclusion</title> <p id="sp0020">The addition of PX-866 to docetaxel did not improve PFS, RR, or OS in patients with advanced, refractory HNSCC without molecular pre-selection.</p> </sec> </abstract>