Table 1.
Summary of all targeted therapies, chemotherapies, and immunotherapies.
| Study | Therapy | Dose * | Target | Histological Subtypes | Sample Size ** | ORR (%) | Complete Response (%) | Partial Response (%) | SD (%) | DP (%) | PFS (Months) | OS (Months) | Toxicity (Most Common) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Phase II | Targeted Therapy | ||||||||||||
| Pfeffer et al. [39] | imatinib | 300–800 mg/d | c-kit, bcr-abl, PDGRF | c-kit positive ACC | 10 | 0 | 0 | 0 | 2 | diarrhea, fatigue, periorbital edema | |||
| Hotte et al. [40] | imatinib | 600–800 mg/d | c-kit, bcr-abl, PDGRF | c-kit positive ACC | 16 | 0 | 0 | 0 | 6 | 6 | 7.5 | rash, headache, dyspnea | |
| Ghosal et al. [41] | imatinib, cisplatin | imatinib 400–800 mg/d, cisplatin 80 mg/m2 | c-kit, bcr-abl, PDGRF | c-kit positive ACC | 28 | 10.3 | 0 | 10.3 | 67.9 | 15 | 35 | anemia, thrombocytopenia, fatigue, facial edema | |
| Wong et al. [42] | dasatinib | 100 mg/d | the c-kit, bcr-abl, SRC family, PDGFß, EPHA2 | c-it posiitive ACC, non-ACC | 54 | 1/0 | 0 | 0 | 48.8/53.8 | 70.7/30.8 | 4.8 | fatigue, nausea, headache | |
| Locati et al. [43] | cetuximab | 200–400 mg/m2 | EGFR | ACC, MEC, myoepihelial, AcCC, cystadenocarcinoma | 30 | 0 | 0 | 0 | 80 | skin rash, pruritus, hair loss | |||
| Jakob et al. [44] | gefitinib | 250 mg/d | EGFR | ACC, non-ACC | 37 | 0 | 0 | 0 | 91.7 | 4.3/2.1 | 25.9/16 | diarrhea, rash, fatigue | |
| Agulnik et al. [45] | lapatinib | 1500 mg/d | HER-2, EGFR | EGFR/HER-2 positive ACC, non-ACC | 62 | 0 | 0 | 0 | 79/47 | 21/53 | diarrhea, fatigue, rash | ||
| Keam et al. [46] | dovtinib | 500 mg/d | VEGFR, FGFR, PDGFR, c-kit | ACC | 32 | 3.1 | 0 | 3.1 | 93.8 | 6 | asthenia, myalgia, diarrhea | ||
| Dillon et al. [47] | dovtinib | 500 mg/d | VEGFR, FGFR, PDGFR, c-kit | ACC | 35 | 0 | 0 | 6 | 65 | 8.2 | 20.6 | fatigue, anorexia, nausea | |
| Chau et al. [48] | sunitinib | 37.5 mg/d | VEGFR, c-kit, PDGFR | ACC | 14 | 0 | 0 | 0 | 78.6 | 18.7 | fatigue, oral mucositis, hypophosphatemia | ||
| Ho et al. [49] | regorafenib | 120–160 mg/d | VEGFR, FGFR, PDGFR | ACC | 38 | 0 | 0 | 0 | 42 | ||||
| Kim at al. [50] | nintedanib | 400 mg (200 mg twice daily) | VEGFR, FGFR, PDGFR | ACC, adenocarcinoma, MEC, SDC, AcCC | 20 | 0 | 0 | 0 | Liver enzyme elevation, nausea | ||||
| Tchekmedyan et al. [51] | lenvatinib | 24 mg/d | VEGFR, FGFR, PDGFR | ACC | 33 | 15.6 | 0 | 15.6 | 75 | 17.5 | hypertension, oral pain | ||
| Locati et al. [52] | lenvatinib | 24 mg/d | VEGFR, FGFR, PDGFR | ACC | 28 | 11.5 | 0 | 11.5 | 9.1 | 27 | asthenia, hypertension, decreased weight | ||
| Locati et al. [53] | axitinib | 10 mg/d | VEGFR, PDGFR, c-Kit | ACC, non-ACC | 26 | 8 | 0 | 8 | 50 | 42 | 5.5 | 26.2 | stomatitis, fatigue, hypertension |
| Ho et al. [54] | axitinib | 10 mg–20 mg/d | VEGFR, PDGFR, c-Kit | ACC, non-ACC | 33 | 9.1 | 0 | 9.1 | 75.8 | 12.1 | 5.7 | hypertension, oral pain, fatigue | |
| Thomson et al. [55] | sorafenib | 800 mg/d | VEGFR, PDGFR, c-Kit | ACC | 23 | 11 | 0 | 11 | 68 | 21 | 11.3 | 19.6 | fatigue, weight loss, hand foot syndrome |
| Locati et al. [56] | sorafenib | 800 mg/d | VEGFR, PDGFR, c-Kit | ACC, non-ACC (adenocarcinoma, SDC, MEC) | 37 | 16 | 0 | 16.2 | 76 | 8.9/4.2 | 26.4/12.3 | ||
| Takahashi et al. [57] | trastuzumab, docetaxel | trastuzumab 6–8 mg/kg, docetaxel 70 mg/m2, q d22 | ErbB2/HER-2 | EGFR-positive SDC | 57 | 70.2 | 8.9 | 39.7 | anemia, decreased EBC, neutropenia | ||||
| Fushimi et al. [58] | leuprorelin, bicalutamide | leuprorelin 3.75 mg, bicalutamide 80 mg | dual androgen-receptor | AR-positive adenocarcinoma, SDC | 36 | 41.7 | 8.8 | 30.5 | elevated liver transaminases, increased serum creatinine | ||||
| Locati et al. [59] | abiraterone | 1 g (plus prednisolone 10 mg, luteinizing hormone-releasing hormone) | androgen-receptor (CYP17A1) | AR-positive SDC | 24 | 21 | 5 | 3.65 | 22.5 | fatigue, flushing, tachycardia | |||
| Ho et al. [60] | enzalutamide | 160 mg/d | androgen-receptor | AR-positive SDC | 46 | 15.2 | 0 | 15.2 | 42.2 | 5.5 | |||
| Chemotherapy | |||||||||||||
| Licitra et al. [61] | cisplatin | 100 mg/m2, q d22 | 18 | 14 | |||||||||
| Licitra et al. [62] | cyclophophamide, doxorubicin, cisplatin (CAP) | cyclophosphamide 500 mg/m2, doxorubicin 80 mg/m2, cisplatin 80 mg/m2, q d28 | ACC, myoepithelioma, SDC, adenocarcinoma, MEC, NEC, undiff. | 22 | 27 | 0 | 27 | 21 | neutropenia, stomatitis | ||||
| Debaere et al. [63] | cyclophophamide, doxorubicin, cisplatin (CAP) | ACC, adenocarcinoma | 15 | 60 | 6.6 | 15.1 | neutropenia, neutropenic fever, alopecia | ||||||
| Laurie et al. [64] | cisplatin, gemcitabine | cisplatin 70 mg/m2 or carboplatin AUC 5 d2, gemcitabine 1000 mg/m2 d1.8, q d22 | ACC, adenocarcinoma, MEC, other | 33 | 24 | nausea, fatigue, hearing loss | |||||||
| Gilbert et al. [65] | paclitaxel | 200 mg/m2 q d22 | ACC, adenocarcinoma, MEC | 45 | 26 | 0 | 26 | leucopenia, granulocytopenia, infection | |||||
| Airoldi et al. [66] | cisplatin plus vinorelbin vs. vinorelbin | vinorelbin 25 mg/m2 d1 and d8, cisplatin 80 mg/m2 d1 vs. vinorelbin 30 mg/m2 weekly | ACC, MEC, adenocarcinoma | 36 | 44/20 | 19/0 | 25/20 | 37.5/45 | 19/35 | nausea | |||
| Hong et al. [67] | vinorelbin, cisplatin | vinorelbin 25 mg/m2 d1 and d8, cisplatin 80 mg/m2 d1, q d22 | ACC, adenocarcinoma, AcCC, MEC, undiff., carcinoma ex pleomorphic adenoma | 40 | 1 | 1 | 0 | 33 | 62 | 6.3 | 16.9 | anemia, leucopenia, neutropenia | |
| Airoldi et al. [68] | vinorelbin, cisplatin | vinorelbin 25 mg/m2 d1 and d8, cisplatin 80 mg/m2 d1, q d22 | adenocarcinoma, undifferentiated | 60 | 51.7 | 7 | 24 | 10 | |||||
| Immunotherapy | |||||||||||||
| Rodriguez et al. [69] (phase II) | pembrolizumab, vorinostat | pembrolizumab 200 mg fixed dose every 3 weeks, vorinostat 400 mg 5 days on, 2 days off | PD-1, histone deacetylase | ACC, AcCC, MEC, adenocarcinoma, SDC | 25 | 4 | 0 | 4 | 6.9 | 14 | renal insufficiency, fatigue, nausea | ||
| Mahmood et al. [70] (phase II) | pembrolizumab vs pembrolizumab, RT | 200 mg fixed dose every 3 weeks | PD-1 | ACC | 20 | 0 | 0 | 0 | 60 | 0/4.5 | 27.2/6.6 | liver enzyme elevation | |
| Cohen et al. [71], Keynote-028 (phase Ib) | pembrolizumab | 10 mg/kg every 3 weeks | PD-1 | PD-L1-positive adenocarcinoma, undifferentiated, MEC, squamous cell ACC | 26 | 12 | 0 | 11.5 | diarrhea, pruritus, fatigue |
In detail, the table contains the first author, citation, therapy and dosage, target, histological subtypes, sample size, and the outcome measures for overall response rate (ORR), complete responses (%), partial responses (%), stable disease (SD), disease progression (DP), progression-free survival (PFS), overall survival (OS), and the most common toxicities. * The column dose contains only the administered dose and not the number of cycles ** The sample size includes all included patients, even if some studies did not administer medication to all included patients.