Preliminary results for the advanced salivary gland carcinoma cohort of the phase 1b KEYNOTE-028 study of pembrolizumab.

Cohen, Roger B.; Delord, Jean‐Pierre; Doi, Toshihiko; Piha‐Paul, Sarina A.; Liu, Stephen V.; Gilbert, Jill; Algazi, Alain P.; Cresta, Sara; Hong, Ruey‐Long; Tourneau, Christophe Le; Day, Daphne; Varga, Andréa; Élez, Elena; Wallmark, John M.; Saraf, Sanatan; Morosky, Anne; Cheng, Jonathan D.; Keam, Bhumsuk

doi:10.1200/jco.2016.34.15_suppl.6017

Cited by 51 publications

(73 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In a clinical trial of 26 patients with PD-L1-positive advanced salivary gland cancer of various histologies, the objective response rate for pembrolizumab monotherapy was only 12%. 22 However, additional trials (NCT03360890) are underway with the hope of achieving improved clinical response rates using combination pembrolizumab plus chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…[19][20][21] While immunotherapy has not yet been clinically validated for the treatment of salivary gland malignancies including SDC, several trials are underway. A study of Cohen et al 22 revealed a modest therapeutic benefit (12% response rate) of pembrolizumab in the patients with PD-L1 positive (≥1% positive cancer or IC) SDC, and it is thought that a combination treatment with chemotherapy may improve the clinical response rates (NCT03360890).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Novel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling

et al. 2019

View full text Add to dashboard Cite

Salivary duct carcinoma (SDC) is a rare, aggressive salivary gland malignancy, which often presents at an advanced stage. A proportion of SDC are characterized by HER2 amplification and/or overexpression of androgen receptor (AR), which could be targeted in a subset of patients, but the presence of AR splice variant‐7 (AR‐V7) in some SDC cases could result in resistance to anti‐androgen therapy. We evaluated a cohort of 28 cases of SDC for potentially targetable biomarkers and pathways using immunohistochemistry (IHC) and next‐generation sequencing (DNA and RNA) assays. Pathogenic genetic aberrations were found in all but 1 case and affected TP53 (n = 19), HRAS (n = 7), PIK3CA, ERBB2 (HER2), and NF1 (n = 5 each); KMT2C (MLL3) and PTEN (n = 3 each); BRAF (p.V600E), KDM5C and NOTCH1 (n = 2 each). Androgen receptor was expressed in all cases and 13 of 27 harbored the AR‐V7 splice variant (including a case without any other detectable genetic alteration). HER2 IHC was expressed in 11 of 28 cases. The majority of SDC cases had no biomarkers predictive of immunotherapy response: 5 cases exhibited low (1%‐8%) programmed death ligand 1 (PD‐L1) expression in tumor cells, 2 cases exhibited elevated TMB, and no samples exhibited microsatellite instability. Notably, the pre‐treatment biopsies from 2 patients with metastatic disease, who demonstrated clinical responses to anti‐androgen therapy, showed AR expression and no AR splice variants. We conclude that comprehensive molecular profiling of SDCs can guide the selection of patients for targeted therapies involving AR, HER2, PD‐L1, mitogen‐activated protein kinase, and PIK3CA pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Novel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Shortly after his disease progressed on dabrafenib and trametinib, preliminary results of the salivary arm of the KEYNOTE-028 trial of pembrolizumab were reported and suggested a possible role for immunotherapy. 30 These data provided a rationale to petition for the use of nivolumab, which was granted. Unfortunately, our patient was unable to tolerate this treatment due to severe fatigue, and it was discontinued.…”

Section: Discussionmentioning

confidence: 99%

First-Line Treatment of Widely Metastatic BRAF-Mutated Salivary Duct Carcinoma With Combined BRAF and MEK Inhibition

Lin¹,

Nabell²,

Spencer³

et al. 2018

J Natl Compr Canc Netw

View full text Add to dashboard Cite

Salivary duct carcinoma (SDC) is a rare and aggressive malignancy for which limited data exist to guide treatment decisions. With the advent of advanced molecular testing and tumor genomic profiling, clinicians now have the ability to identify potential therapeutic targets in difficult-to-treat cancers such as SDC. This report presents a male patient with widely metastatic SDC found on targeted next-generation sequencing to have a BRAF p.V600E mutation. He experienced a prolonged and robust response to first-line systemic chemotherapy with dabrafenib and trametinib. During his response interval, new data emerged to justify subsequent treatment with both an immune checkpoint inhibitor and androgen blockade after his disease progressed. To our knowledge, this is the first report of frontline BRAF-directed therapy eliciting a response in metastatic SDC.

show abstract

“…Large federally funded, site‐agnostic, genomic profiling‐based basket studies, such as Molecular Analysis for Therapy Choice (MATCH; NCT02465060) and Targeted Agent and Profiling Utilization Registry (TAPUR; NCT02693535), are ongoing, and results of these may further support this approach for salivary gland cancers. In addition, novel therapeutics involving immune checkpoint inhibition are being explored in this disease, and early reports from single agent pembrolizumab suggests that a small subset may benefit from this approach …”

Section: Discussionmentioning

confidence: 99%

Phase II trial of eribulin mesylate in recurrent or metastatic salivary gland malignancies

et al. 2017

View full text Add to dashboard Cite

show abstract

Preliminary results for the advanced salivary gland carcinoma cohort of the phase 1b KEYNOTE-028 study of pembrolizumab.

Cited by 51 publications

References 0 publications

Novel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling

Novel therapeutic targets in salivary duct carcinoma uncovered by comprehensive molecular profiling

First-Line Treatment of Widely Metastatic BRAF-Mutated Salivary Duct Carcinoma With Combined BRAF and MEK Inhibition

Phase II trial of eribulin mesylate in recurrent or metastatic salivary gland malignancies

Contact Info

Product

Resources

About