The effectiveness of targeted therapy for recurrence or metastasis adenoid cystic carcinoma: a systematic review and meta-analysis

Abstract

Background and purpose: Several clinical studies have demonstrated the potential of molecular-targeted agents for the treatment of recurrent or metastatic adenoid cystic carcinoma (R/M ACC). However, there is currently no consensus regarding the efficacy of molecular-targeted agents for patients with R/M ACC. This study aimed to evaluate the therapeutic efficacy and safety of molecular-targeted agents in patients with R/M ACC and provide insights to guide clinical decision-making.

Materials and methods: Five databases (PubMed, Embase, Cochrane, ProQuest, and Scopus) were searched based on the search strategy and selection criteria. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints were disease control rate (DCR), overall survival (OS), metastatic sites, and adverse events (AE). Pooled estimates were calculated using a random-effects meta-analysis.

Results: Finally, 28 studies, involving 849 patients, were included. The most common metastatic sites were the lungs, bones, liver, lymph nodes, and kidneys. The pooled ORR was 4.0% (95% CI, 0.7-8.8%), the pooled DCR was 80.5% (95% CI, 72.2%-87.7%). Compared with other-target drugs, multiple kinase inhibitors (MKIs) improved the ORR (pooled ORR for single-target drugs vs. MKIs: 5.9% vs. 0%). The combination of MKIs and immune checkpoint inhibitors (ICIs) had a significantly higher ORR (17.9% in the axitinib + avelumab group). The pooled median PFS and OS were 8.35 and 25.62 months, respectively. MKIs improved the median PFS compared to other-target drugs (9.43 months vs 5.06 months). In addition, the most common adverse events (AEs) were fatigue (51.6%), hypertension (44.2%), and nausea (40.0%), followed by hand-foot skin syndrome (36.8%), diarrhoea (34.4%), weight loss (34.2%), anorexia (31.8%), rash (31.7%), and headache (29.0%).

Conclusion: The findings of this study suggest that MKIs have a better therapeutic efficacy than single-target drugs in patients with R/M ACC. Future studies are warranted to verify the synergistic role of the combination strategy of MKIs plus ICIs, given the limited number of studies on this topic conducted and published to date.

Keywords: Adenoid cystic carcinoma; meta-analysis; multiple kinase inhibitors; targeted therapy.

Figure 1.

Flow diagram of included and excluded studies.

Figure 2.

Pooled results of ORR represented by Forest plots. The large diamond at the bottle of the plot represents the pooled rate of all studies. The width of the diamond represents with 95% CI.

Figure 3.

Pooled results of DCR by Forest plots. The large diamond at the bottle of the plot represents the pooled rate of all studies. The width of the diamond represents with 95% CI.

Figure 4.

Pooled Kaplan-Meier survival curves of ACC treated with targeted therapy. (A) Pooled Kaplan-Meier PFS curves of ACC targeted therapy; (B) Pooled Kaplan-Meier OS curves of ACC targeted therapy; (C) Pooled summary progression-free survival curves of ACC treated with single-target targeted therapies; (D) Pooled summary progression-free survival curves of ACC treated with MKI targeted therapies. Blue lines represent survival curves for individual studies. Solid red lines represent summary survival curves with 95% CIs (dashed red lines).