Abstract 2275
Background
MSGT are rare with limited systemic treatments. This ongoing trial is a single-institution, prospective study in advanced MSGT involving 2 phases: genomic profiling followed by treatment with either genomically-matched or unmatched therapy. The aim is to determine response rates as per RESIST v1.1 in patients (pts) with MSGT treated with matched or unmatched therapy.
Methods
Pts with recurrent/metastatic MSGT with archived paraffin-embedded tumor samples were enrolled in the profiling phase. Following pathology review and DNA extraction, targeted next generation sequencing was performed in a CLIA certified laboratory. Immunohistochemistry for androgen receptor (AR) and fluorescence in-situ hybridization for HER2 and ALK was done. Successfully profiled pts then proceeded to treatment phase when their disease was progressing to receive a matched therapy via early phase clinical trials or approved agents. If no actionable mutations were identified or no matched agents were available, pts could receive selinexor, an oral selective inhibitor of nuclear export (SINE) that inhibits XPO1 at a dose of 60mg twice weekly. Non-progressing pts remained on active surveillance.
Results
Since July 2014, 38 pts (19M/19F, median age 62 yrs [range 37-85]) have been enrolled in the profiling phase. Disease subtypes include adenoid cystic (n = 19), salivary duct (n = 8) and other (n = 11). Four pts failed screening due to lack of tissue, 4 tumor samples are currently being analysed. Of the 30 evaluable pts, 13 (43%) had at least one actionable mutation. Aberrations identified include PIK3CA (6), TP53 (5), AR (4), BRAF (2), HRAS (2), HER2 amplification (1), HER2 mutation (1), KIT (1), EGFR (1) and PTEN (1). Eight pts were treated with genomically matched therapy and 7 received selinexor. See table for outcomes.Table: 1078P
| Matched Treatment | Selinexor | |
|---|---|---|
| Median Duration of treatment | 9 months (mo) | 4mo |
| Median overall survival | 19.2mo | 21.3mo |
| Stable disease rate | 88% (7/8) | 86% (6/7) |
| Progressive disease rate | 12% (1/8) | 14% (1/7) |
Conclusions
Genomic profiling may be integrated into clinical care for pts with MSGT permitting pts to receive targeted therapy. This is an ongoing study, we will present updated data at the conference.
Clinical trial identification
NCT02069730.
Legal entity responsible for the study
Princess Margaret Cancer Center.
Funding
Princess Margaret Cancer Center/Karyopharm.
Editorial Acknowledgement
Disclosure
A. Spreafico: Consultant and advisory board: Merck, BMS, Novartis; Research support to UHN: Karyopharm. A. Hansen: Research support: Genentech/Roche, Merck, GlaxoSmithKline, Bristol-Myers Squibb, Novartis, Boston Biomedical, Boehringer-Ingelheim, Karyopharm. All other authors have declared no conflicts of interest.
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