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Clinical Studies

Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review of the last decade

British Journal of Cancer volume 131, pages 1021–1031 (2024)Cite this article

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Abstract

Importance

Recurrent/metastatic adenoid cystic carcinoma (R/M AdCC) presents a clinical challenge with limited treatment options, particularly in the face of unsatisfactory efficacy from current therapeutic approaches. This review underscores the unmet clinical needs in managing R/M AdCC, emphasising the imperative for novel therapeutic strategies to address this critical gap.

Objective

The primary objective of this review is to comprehensively analyse and assess trials investigating therapeutic approaches for R/M AdCC. Emphasis is placed on endpoints such as tumour response rates and progression-free survival. The specific interventions, populations, and outcomes examined in these trials will be detailed to provide a focused and informative systematic review.

Evidence review

The systematic search spanned databases, including PubMed, EMBASE, and the Cochrane database of systematic reviews. Employing terms like “Carcinoma, Adenoid Cystic” and “trial,” the search focused on English full-text articles from April 1, 2010, to August 9, 2023. Inclusion criteria encompassed studies with patients having R/M AdCC, involving drug interventions. Study quality was assessed using the Newcastle–Ottawa Scale for retrospective studies, Cochrane ROBINS-I tool for non-randomised trials, and the ROB-2 tool for randomised controlled trials.

Findings

A total of 46 trials involving 1244 patients are included in this review, encompassing a variety of therapeutic approaches for R/M AdCC. Targeted therapies, particularly Apatinib at 500 mg, exhibit efficacy with a 47.1% objective response rate (ORR). Conversely, immunotherapeutic agents demonstrate suboptimal performance, with an overall ORR ranging from 0 to 18%. While Apatinib shows promise, the review underscores the imperative for a thorough exploration of drugs targeting unique mechanisms in the immunologically cold nature of R/M AdCC.

Conclusions and relevance

Substantial progress in systemic therapy for R/M AdCC is evident, driven by early-phase clinical trials, particularly with promising outcomes in VEGF-2 inhibitors. However, challenges persist, notably in immunotherapy due to the cancer’s immunologically cold nature. Ongoing research, prioritising early-stage trials, is crucial, emphasising exploration of emerging therapies like cell therapy and antibody–drug conjugates. Transitioning to Phase III trials is essential for more precise therapeutic insights. Collaborative efforts and a focus on personalised precision medicine are vital for overcoming challenges and advancing our understanding of treatment efficacy in this rare cancer.

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Fig. 1: Flowchart of study selection.

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Funding

This work was supported by the grant Beijing Municipal Health Commission (Beijing Demonstration Research Ward BCRW20200303); National Natural Science Foundation of China (Mechanism investigation of CAR-γδT cells therapy in the treatment of malignant pleural mesothelioma, 82272951); National Natural Science Foundation of China (Mechanism exploration of hybrid membrane vaccine for immunotherapy of malignant schwannomas, 82272953); Chinese Academy of Medical Sciences (2022-I2M-C&T-B-070).

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  1. These authors contributed equally: Jiawei Zhou, Guo Zhao.

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  1. Clinical Cancer Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Jiawei Zhou, Guo Zhao, Shuhang Wang & Ning Li

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J Zhou and G Zhao wrote the first draft, prepared the figures and edited the final version. S Wang and N Li contributed to the revision. All the authors have seen and approved the final version.

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Zhou, J., Zhao, G., Wang, S. et al. Systemic therapy in the management of metastatic or locally recurrent adenoid cystic carcinoma of the salivary glands: a systematic review of the last decade. Br J Cancer 131, 1021–1031 (2024). https://doi.org/10.1038/s41416-024-02795-4

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