Systemic therapy in metastatic salivary gland carcinomas: A pathology-driven paradigm?

Alfieri, Salvatore; Granata, Roberta; Bergamini, Cristiana; Resteghini, Carlo; Bossi, Paolo; Licitra, Lisa; Locati, Laura D.

doi:10.1016/j.oraloncology.2016.12.016

Cited by 101 publications

(114 citation statements)

References 65 publications

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“…Histologic subtypes of salivary gland cancers can be segregated by the expression of specific molecular markers and may accordingly respond differently to conventional and targeted chemotherapeutic agents. 2 For instance, ACC tends to express the receptor tyrosine kinase (RTK) c-Kit and is known to be poorly responsive to not only conventional chemotherapy 3 but also TKIs with activity against c-Kit, such as imatinib 4 and dasatinib. 5 In contrast, a recent retrospective review of patients with SDC suggested a benefit to treatment with combined carboplatin and paclitaxel.…”

Section: Discussionmentioning

confidence: 99%

“…9 Therefore, it only rarely expresses estrogen or progesterone receptors, but has been associated with expression of HER2 and AR, both of which might be markers for response to targeted therapies. 2 Retrospective studies have suggested that targeting HER2 with trastuzumab may be of benefit in HER2-expressing SDC, 10 and interim results from a prospective phase II trial of docetaxel plus trastuzumab were encouraging. 11 Furthermore, a recent case report suggested that trastuzumab emtansine (T-DM1) may have utility after trastuzumab failure.…”

Section: Discussionmentioning

confidence: 99%

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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

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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.

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Section: Discussionmentioning

confidence: 99%

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

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“…The approach to the incurable recurrent or metastatic patient is unclear, due to the great biological heterogeneity, which is highly histology‐dependent. Responses to systemic agents in unselected patients are generally modest . As randomized controlled studies are lacking, treatment selection in SGCs should be made on a more personalized approach.…”

Section: Introductionmentioning

confidence: 99%

“…Inoperable or metastatic ACCs can have an indolent course, and watchful waiting is the most common approach . When treatment is warranted, a response rate of 15% to 70% is achieved with cisplatin and 15.4% with vinorelbine .…”

Section: Introductionmentioning

confidence: 99%

Next‐generation sequencing in salivary gland carcinoma: Targetable alterations lead to a therapeutic advantage—Multicenter experience

et al. 2019

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Background Salivary gland cancers (SGCs) are rare. The approach to metastatic patients is histology‐dependent. There is little evidence on whether next‐generation sequencing (NGS) findings translate to tumor control in SGCs. Methods We analyzed all patients with histologically confirmed SGC who underwent NGS. Results Twenty‐seven patients were identified, 14 (51.8%) had targetable findings in NGS: 5 ERBB2 amplifications, 3 PIK3CA mutations, 2 RUNX1 mutations, 1 TRIM33‐RET fusion, 1 FGFR3‐TACC3 fusion, 1 microsatellite instability‐high, and 2 high mutational burden. Ten patients were treated accordingly. Median progression‐free survival for targeted treatment was 8.4 months. Of five patients who achieved durable responses of 8.4 to 31.3 months, two are ongoing. The overall median survival was not reached for patients receiving targeted treatment and was 40.4 months for patients treated conventionally (P = .18). Conclusions In the absence of a well‐established therapeutic approach, NGS may detect clinically significant genetic alterations and benefit patients with advanced SGC.

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“…For instance, ACC's indolent behavior is explained by its scarce genetic instability whereas salivary duct carcinomas are characterized by a high mutation rate and the expression of androgen receptor . Therefore, this latter type of PC has an aggressive clinical course yet promising trials are being conducted using androgen‐deprivation therapy . Even more recently, it has been demonstrated how programmed death‐1 ligand‐1 (PD‐L1) expression can significantly predict outcomes and the risk of developing DM .…”

Section: Discussionmentioning

confidence: 99%

A nomogram to estimate the risk of developing distant metastases in parotid cancer

et al. 2019

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Background Parotid cancer (PC) is a heterogeneous group of malignant tumors whose management mainly focuses on locoregional control. However, distant metastases (DM) can represent the most common cause of treatment failure. We have defined the predictors and developed a model that can predict a single patient's risk to develop DM. Methods We have analyzed our institutional database of 259 patients with PC and use it to develop a nomogram. C‐index and calibration curves were used to assess performance of our model. Results DM appeared in 18.9% of patients. Age, cT, pN, perineural invasion, and adenoid cystic carcinoma were significantly associated with distant failure. Conclusions We here present the first model to identify patients with PC at high risk of DM. Such tool can be of great value in managing these rare cancers in terms of a more precise prognosis and follow‐up while waiting for better systemic therapies to come in the future.

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Systemic therapy in metastatic salivary gland carcinomas: A pathology-driven paradigm?

Cited by 101 publications

References 65 publications

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

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

Next‐generation sequencing in salivary gland carcinoma: Targetable alterations lead to a therapeutic advantage—Multicenter experience

A nomogram to estimate the risk of developing distant metastases in parotid cancer

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