Presence of both alterations in FGFR/FGF and PI3K/AKT/mTOR confer improved outcomes for patients with metastatic breast cancer treated with PI3K/AKT/mTOR inhibitors
Jennifer J. Wheler1, Johnique T. Atkins2, Filip Janku2, Stacy L. Moulder3, Philip J. Stephens4, Roman Yelensky4, Vicente Valero3, Vincent Miller4, Razelle Kurzrock5, Funda Meric-Bernstam2
1Translational clinical oncology, Novartis Pharmaceuticals, Cambridge, MA, USA
2Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
3Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
4Foundation Medicine, Cambridge, MA, USA
5The Center for Personalized Cancer Therapy, University of California San Diego Moores Cancer Center, La Jolla, CA, USA
Correspondence to:
Johnique T. Atkins, email: [email protected]
Keywords: breast cancer, FGFR, next-generation sequencing, PI3K
Received: March 22, 2016 Accepted: May 13, 2016 Published: June 09, 2016
ABSTRACT
There is limited data on co-expression of FGFR/FGR amplifications and PI3K/AKT/mTOR alterations in breast cancer. Tumors from patients with metastatic breast cancer referred to our Phase I Program were analyzed by next generation sequencing (NGS). Genomic libraries were selected for all exons of 236 (or 182) cancer-related genes sequenced to average depth of >500× in a CLIA laboratory (Foundation Medicine, Cambridge, MA, USA) and analyzed for all classes of genomic alterations. We report genomic profiles of 112 patients with metastatic breast cancer, median age 55 years (range, 27-78). Twenty-four patients (21%) had at least one amplified FGFR or FGF. Fifteen of the 24 patients (63%) also had an alteration in the PI3K/AKT/mTOR pathway. There was no association between alterations in FGFR/FGF and PI3K/AKT/mTOR (P=0.49). Patients with simultaneous amplification in FGFR/FGF signaling and the PI3K/AKT/mTOR pathway had a higher rate of SD≥6 months/PR/CR when treated with therapies targeting the PI3K/AKT/mTOR pathway than patients with only alterations in the PI3K/AKT/mTOR pathway (73% vs. 34%; P=0.0376) and remained on treatment longer (6.8 vs. 3.7 months; P=0.053). Higher response rates were seen in patients with simultaneous amplification in FGFR/FGF signaling and alterations in the PI3K/AKT/mTOR pathway who were treated with inhibitors of that pathway.
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