Evaluation of pembrolizumab monotherapy in patients with previously treated advanced salivary gland carcinoma in the phase 2 KEYNOTE-158 study

Even, Caroline; Delord, Jean‐Pierre; Price, Katharine A.; Nakagawa, Kazuhiko; Oh, Do‐Youn; Burge, Matthew; Chung, Hyun Cheol; Doi, Toshihiko; Fakih, Marwan; Takahashi, Shunji; Yao, Lili; Jin, Fan; Norwood, Kevin; Hansen, Aaron Richard

doi:10.1016/j.ejca.2022.05.007

Cited by 25 publications

(26 citation statements)

References 19 publications

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“…Few prospective clinical trials have investigated the use of ICPi for patients with SGC. Among results, e cacy in patients with ACC was modest [12][13][14][15]. In our study, ACC showed not only lower in ltration of immune effector cells such as CD3 + CD4 + T cells and CD3 + CD8 + T cells but also lower in ltration of immune suppressor cells such as CD3 + CD4 + Foxp3 + cells (regulatory T cells) and CD204 + cells (M2 macrophages) compared with other pathological types.…”

Section: Discussionmentioning

confidence: 55%

“…These ICPi have been proven effective not only in malignant melanoma but also in non-small cell lung cancer, renal cell carcinoma, head and neck squamous cell carcinoma, esophageal cancer, gastric cancer, and microsatellite instability-high cancers [5][6][7][8][9][10][11]. For SGC, the e cacy of ICPi has not been elucidated, while some previous studies reported that ICPi might be less effective for ACC [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

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Different characteristics of the tumor immune microenvironment among subtypes of salivary gland cancer

Nagatani

Kiyota

Imamura

et al. 2023

Preprint

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Although immune checkpoint inhibitors (ICPi) for salivary grand cancer (SGC) have been investigated in clinical trials, details of the tumor immune microenvironment (TIME) remain unclear. This research aimed to elucidate the TIME of SGC and its relationship with tumor mutation burden (TMB) and to explore the rationale for the applicability of ICPi. We selected five pathological types, namely adenoid cystic carcinoma (ACC); adenocarcinoma, not otherwise specified (ANOS); salivary duct carcinoma (SDC); and low/high-grade mucoepidermoid carcinoma (MEClow/high). We investigated the TIME and TMB of each pathological type. TIME was evaluated by multiplexed fluorescent immunohistochemistry. TMB was measured by next-generation sequencing. ACC and MEChigh showed the lowest and higher infiltration of immune effector and suppressor cells in both tumor and stroma. ANOS, SDC, and MEClow showed modest infiltration of immune effector cells in tumor. Correlation analysis showed a positive correlation between CD3+CD8+ T cells in tumor and TMB (r = 0.647). CD3+CD8+ T cells in tumor showed a positive correlation with PD-L1 expression in tumor cells (r = 0.513) and a weak positive correlation with CD3+CD4+Foxp3+ cells in tumor (r = 0.399). However, no correlation was observed between CD3+CD8+ T cells and CD204+ cells in tumor (r = -0.049). The TIME of ACC was the so-called immune desert type, which may explain the mechanisms of the poor response to ICPi in previous clinical trials. On the other hand, MEChigh was the immune inflamed type, and this may support the rationale of ICPi for this pathological subtype.

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Section: Discussionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Different characteristics of the tumor immune microenvironment among subtypes of salivary gland cancer

Nagatani

Kiyota

Imamura

et al. 2023

Preprint

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“…There are different criteria for re-staging of non-small cell lung cancer based on the different treatment that the patient is receiving. Regarding immunotherapy due to the pseudo-progression new criteria had to be created the immune recist criteria [ 28 ]. In the case of hepatitis, colitis and thyroiditis the diagnosis can be made due to the laboratory findings and clinical findings, however; regarding pneumonitis there is still an issue.…”

Section: Discussionmentioning

confidence: 99%

“…Non-small cell lung cancer is still diagnosed at advanced stage and systemic treatment administration is required. We have nowadays novel tools for the diagnosis and staging of lung cancer like radial-ebus, electromagnetic navigation and convex probe-ebus [ [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] ]. However; we still need a successful lung cancer screening program for early lung cancer diagnosis [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Cryobiopsy for pneumonitis diagnosis in NSCLC immunotherapy

Kosmıdis

Perdikouri

Hohemforst-Schmidt

et al. 2022

Respiratory Medicine Case Reports

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“…Seen the involvement of the above-mentioned targets in SGMs, there is strong rationale for the development and testing of specific inhibitors as anti-cancer therapy in SGMs. Multiple clinical studies, of which the majority phase II studies (listed in Table 3 ), have been conducted in order to determine the effectiveness of these inhibitors in heterogeneous populations of SGMs [ 81 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 ].…”

Section: Systemic Therapiesmentioning

confidence: 99%

The Therapeutic Landscape of Salivary Gland Malignancies—Where Are We Now?

Cleymaet

Vermassen

Coopman

et al. 2022

IJMS

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Salivary gland malignancies (SGMs) account for less than 5% of new diagnoses in head and neck tumors. If feasible, surgery is the preferred treatment modality. Nevertheless, some malignancies have a tendency of recurrence, with possible distant metastasis. Alternative treatment strategies, such as primary radiation or chemotherapeutics, often present low response rates. As a result, there is an unmet need for novel therapeutic approaches. Nowadays, target-based therapies (e.g., small inhibitors and immunotherapy) are used by the medical oncologist for possible treatment of advanced SGMs. Based on recent published trials, some novel treatments may provide additional disease control for some patients. However, sample sizes are small, the general findings are unsatisfactory, and a lot of uncertainties remain to be elucidated. Nevertheless, research shows that patients do not benefit from blind administration of systemic treatments and therefore a more personalized approach is highly needed. The aim of this review paper is to summarize the most recent advances in the biological understanding and molecular pathways of salivary gland cancers the association of these pathways with the current treatments used and their implications for more personalized targeted-based therapies.

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Evaluation of pembrolizumab monotherapy in patients with previously treated advanced salivary gland carcinoma in the phase 2 KEYNOTE-158 study

Cited by 25 publications

References 19 publications

Different characteristics of the tumor immune microenvironment among subtypes of salivary gland cancer

Different characteristics of the tumor immune microenvironment among subtypes of salivary gland cancer

Cryobiopsy for pneumonitis diagnosis in NSCLC immunotherapy

The Therapeutic Landscape of Salivary Gland Malignancies—Where Are We Now?

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