Effective systemic therapies are lacking for mSGT and no standard EMA-approved agents are available. Molecular alterations can guide targeted therapeutics, but the value of comprehensive genomic/proteomic profiling to detect clinically relevant targeteable alterations (TA) as per ESCAT remains to be studied.
We analyzed all mSGT pts treated at VHIO phase I Unit from 2016 to 2019. Clinicopathological features, molecular alterations and treatment modalities were correlated with outcomes (objective response rates [ORR] and progression-free survival [PFS]). Clinical actionability of multigene panel testing (NGS) and immunohistochemistry (IHC) was defined as per ESCAT scale.
In total 107 pts with baseline NGS were identified, median age was 56.7 years, 93 pts (86.9%) ECOG ≤1, primary tumor histology was adenoid cystic carcinoma in 47%, salivary duct carcinoma in 13%, myoepithelial carcinoma in 8%, other in 32%. Median number of treatment lines was 1.5 (range 0-10), median overall survival was 51.5 months (m) (95%CI 33.9-NA) and median follow-up 25.5 m. On IHC, HER2 overexpression in 7%, Androgen Receptor (AR) in 43% and Estrogen/Progesterone Receptor (ER/PR) in 12%. On NGS, PIK3CA mut in 7%, NOTCH1 mut in 6%, FGFR1-3 mut in 5%, NTRK fusion in 4%. Out of 11 samples with tumor mutation burden assessed, all were low (median=2.5 mut/Mb, range 0-5). According to ESCAT, 48 pts (45%) showed at least one TA and 29 (27%) were treated accordingly. In total, 20 ESCAT levels 1/2 therapies (1 NTRK, 6 HER2, 13 RA) and 13 ESCAT levels 3/4 therapies (2 RE/RP, 5 PIK3CA, 3 FGFR, 1 EGFR, 2 NOTCH) were tested. ORR was 30%, with a trend for higher ORR in level 1/2 vs. 3/4 (Odds ratio 9.8, p= 0.058). Median PFS on TA was 5 months (CI95% 3.45-19.04), not different as per ESCAT levels (3.4 months vs. 12.4 months, hazard ratio 0.6, p= 0.23).
In our cohort, molecularly-guided TA have promising activity in pts with mSGT. These results suggest that MGT and IHC tests are of potential value in selected populations. Response rates are higher with therapies matched to ESCAT level 1/2 alterations, but long-term disease control can also be achieved with more emerging actionability markers levels 3/4.
Clinical trial identification
Legal entity responsible for the study
Vall d´Hebron Institute of Oncology.
Comprehensive Program of Cancer Immunotherapy and Immunology (CAIMI) supported by the Banco Bilbao Vizcaya Argentaria Foundation (BBVA Foundation) (grant 89/2017). -La Caixa Foundation (LCF/PR/CEO7/50610001). Cellex Foundation providing research facilities and equipment.
A. Hernando-Calvo: Travel/Accommodation/Expenses: Kyowa Kirin. A.B. Azaro Pedrazzoli: Advisory/Consultancy: Orion Pharma; Advisory/Consultancy, Research grant/Funding (self): Amcure GmbH. M. Vieito: Advisory/Consultancy: Debio; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: TFS; Travel/Accommodation/Expenses: Merck Serono. O. Saavedra Santa Gadea: Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Kyowa Kirin. R. Dienstmann: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Servier; Speaker Bureau/Expert testimony: Sanofi; Speaker Bureau/Expert testimony: Merck Sharp and Dohme; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Pierre Fabre. E. Felip: Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Janssen; Speaker Bureau/Expert testimony: Medscape; Advisory/Consultancy: Merck KGaA; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Speaker Bureau/Expert testimony: priME Oncology; Advisory/Consultancy: Roche; Advisory/Consultancy: Samsung; Advisory/Consultancy: Takeda; Speaker Bureau/Expert testimony: Touchime; Advisory/Consultancy: GSK; Advisory/Consultancy: Bayer; Research grant/Funding (institution): Grant for Oncology Innovation (GOI); Research grant/Funding (institution): Fundación Merck Salud. E. Garralda: Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Thermo Fisher; Advisory/Consultancy: F. Hoffmann La Roche; Advisory/Consultancy: Ellipses Pharma; Advisory/Consultancy: Neomed Therapeutics1 Inc; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Janssen Global Services; Advisory/Consultancy: SeaGen; Advisory/Consultancy: TFS; Advisory/Consultancy: Alkermes; Advisory/Consultancy: Thermo Fisher; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Merck Sharp and Dohme. I. Braña: Advisory/Consultancy, Leadership role: Orion Pharma; Speaker Bureau/Expert testimony, Leadership role: BMS; Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses: AstraZeneca; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck Serono; Advisory/Consultancy, Leadership role: Rakutan Pharma; Speaker Bureau/Expert testimony: Roche; Leadership role: Celgene; Leadership role: Gliknik; Leadership role: GSK; Leadership role: Janssen; Leadership role: KURA; Leadership role: MSD; Leadership role: Novartis; Leadership role: Pfizer; Leadership role: Shattuck; Leadership role: Northern Biologics; Leadership role: Nanobiotics. All other authors have declared no conflicts of interest.