Molecular profiling and targeted agents in recurrent, metastatic salivary gland tumor (R/M SGT) patients (pts) treated at two academic centers.

Abstract

6081 Background: Treatment selection based on actionable alterations (AAs) is an appealing strategy for pts with R/M SGT. The GEMS-001 study (NCT02069730) at Princess Margaret Cancer Centre (PM) and the Vall D´Hebron Institute of Oncology (VHIO) pre-screening program facilitate the identification of AAs for R/M SGT pts and treatment selection. Methods: We analyzed R/M SGT treated at PM and VHIO from 2015 to 2020. Clinicopathological features, molecular alterations and treatment modalities were correlated with outcomes. The primary endpoint was overall response rate (ORR) by RECIST 1.1. Clinical benefit rate (CBR) was defined by pts with partial response or stable disease ≥4 months. Clinical actionability of multigene panel testing (NGS) and immunohistochemistry (IHC) were assessed as per institutional molecular tumor boards or investigators. Pts were opportunistically matched to available therapies from each center. Results: In total 206 pts were enrolled. On IHC, HER2 overexpression was present in 9%, Androgen Receptor (AR) 33%, Estrogen/Progesterone Receptor (ER/PR) 11% and ALK overexpression 0%. On NGS, PIK3CA mutation (mut) was in 9%, NTRK fusion 6%, NOTCH1-3 mut 5%, HRAS mut 6%, ERBB2/3 alterations (alt) 4% and FGFR1-4 alt 3%. Up to 92 pts (45%) displayed at least 1 AA and 36 pts (18%) had ≥2 AAs. A total of 60 pts (29%) were matched to AAs. Of those matched, median age was 60 years (range 33-84), M:F 21:39, 95% ECOG≤1 with a median number of prior treatment lines 0 (range 0-3), and their AAs included 26 AR, 9 HER2 or ERBB2 overexpression, 9 PIK3CA mut, 3 NTRK fusion, 3 FGFR1-3 alt and 10 other AAs (2 ER/PR overexpression, 2 EGFR mut, 1 c-kit mut, 1 BAP1 mut, 1 Non-V600 BRAF mut, 1 CDKN2A mut, 1 CHEK2 mut and 1 PTCH1 mut). Overall, ORR was 27% for the matched population. See table for outcomes. Conclusions: In our cohort, almost one third of the population received therapies matched to AAs. Our results suggest that targeted therapies have promising activity in pts with R/M SGT supporting comprehensive molecular and IHC profiling in treatment determination.[Table: see text]

Selinexor for the treatment of recurrent or metastatic salivary gland tumors: Results from the GEMS‐001 clinical trial

“…However, despite these advances, the majority of patients will not have actionable alterations on multigene panel testing and thus may not benefit from molecularly targeted approaches. 19 Furthermore, the lack of access to clinical trials testing targeted therapies may also be a barrier for treatment. Consequently, there is an urgent need to identify treatments that are broadly effective in an unselected population of patients with SGT.…”

“…Recently, the understanding of molecular aberrations in SGT has revealed promising targets for matched therapeutics which include NTRK inhibitors and HER‐2 or AR blockade. However, despite these advances, the majority of patients will not have actionable alterations on multigene panel testing and thus may not benefit from molecularly targeted approaches 19 . Furthermore, the lack of access to clinical trials testing targeted therapies may also be a barrier for treatment.…”

“…If after enrollment of the first 18 patients evaluable by RECIST 1.1 no responses were observed, then no further accrual would occur in this phase. This study included a matched cohort arm for patients treated with molecularly targeted agents that has been reported separately and a molecularly unmatched cohort arm investigating selinexor reported here 19 . However, this study was not designed to statistically compare the efficacy between the group of patients receiving selinexor versus matched therapies.…”

Selinexor for the treatment of recurrent or metastatic salivary gland tumors: results from the GEMS-001 clinical trial.

“…If after enrollment of the rst 18 patients evaluable by RECIST 1.1 no responses were observed, then no further accrual would occur in this phase. This study included a matched cohort arm for patients treated with molecularly targeted agents that has been reported separately and a molecularly unmatched cohort arm investigating selinexor reported here 20 . However, this study was not designed to statistically compare the e cacy between the group of patients receiving selinexor vs matched therapies.…”

“…Recently, the understanding of molecular aberrations in SGT has revealed promising targets for matched therapeutics which include NTRK inhibitors and HER-2 or AR blockade. However, despite these advances, the majority of patients will not have actionable alterations on multigene panel testing and thus may not bene t from molecularly targeted approaches 20 . Furthermore, the lack of access to clinical trials testing targeted therapies may also be a barrier for treatment.…”