Introduction: Due to the rarity and various histological types, a standard chemotherapy regimen for recurrent or metastatic salivary gland carcinoma (SGC) has not been established. Molecular-targeted therapy is a novel cancer therapy based on the expression of target molecules. However, few molecular-targeted therapy types have shown satisfactory efficacy for patients with SGC. Our study described promising results of epidermal growth factor receptor (EGFR)-targeting therapy with paclitaxel in patients with SGC. Methods: The medical records of patients with recurrent SGC treated with weekly cetuximab combined with paclitaxel (Cmab-PTX) between December 2017 and December 2022 at our institutions were retrospectively analyzed. Results: Seven patients with SGC received Cmab-PTX therapy. The median age was 76 years. All patients were high-grade histological types, and EGFR expression was positive in all examined patients. Cmab-PTX was administered for a median period of 20 months (range of 2–36 months). The overall responses were three with complete response, two with partial response, one with stable disease (>24 weeks), and one with progressive disease. The objective response and disease control rates were 71.4% and 85.7%, respectively. Progression-free survival ranged between 2 and 36 months (median 12 months), whereas overall survival ranged between 4 and 111 months (median 36 months). One patient experienced a grade 4 adverse event (neutropenia), which was conservatively manageable. Conclusion: Although the treatment sensitivity of SGC with high-grade histological types is usually poor, Cmab-PTX could be a promising treatment regimen for recurrent SGC. Due to the rarity and various histological types, a standard chemotherapy regimen for recurrent or metastatic salivary gland carcinoma (SGC) has not been established. Molecular-targeted therapy is a novel cancer therapy based on the expression of target molecules. However, few molecular-targeted therapy types have shown satisfactory efficacy in patients with SGC. Our study described promising results of cetuximab (Cmab), epidermal growth factor receptor (EGFR)-targeting therapy with paclitaxel (PTX) in patients with SGC. Seven patients with SGC received Cmab-PTX therapy. The median age was 76 years. All patients were high-grade histological types, and EGFR expression was positive in all examined patients. Cmab-PTX was administered for a median period of 20 months. The overall responses were three with complete response, two with partial response, one with stable disease (>24 weeks), and one with progressive disease. The objective response rate was 71.4%. Progression-free survival ranged between 2 and 36 months (median 12 months), whereas overall survival ranged between 4 and 111 months (median 36 months). One patient experienced a grade 4 adverse event (neutropenia), which was conservatively manageable. Our study revealed a preferable objective response rate of Cmab-PTX for patients with high-grade SGC. Although the treatment sensitivity of SGC with high-grade histological types is usually poor, Cmab-PTX could be a promising treatment regimen for recurrent SGC.

Due to the rarity and various histological types, a standard chemotherapy regimen for recurrent or metastatic salivary gland carcinoma (SGC) has not been established. Molecular-targeted therapy is a novel cancer therapy based on the expression of target molecules. However, few molecular-targeted therapy types have shown satisfactory efficacy in patients with SGC. Our study described promising results of cetuximab (Cmab), epidermal growth factor receptor (EGFR)-targeting therapy with paclitaxel (PTX) in patients with SGC. Seven patients with SGC received Cmab-PTX therapy. The median age was 76 years. All patients were high-grade histological types, and EGFR expression was positive in all examined patients. Cmab-PTX was administered for a median period of 20 months. The overall responses were three with complete response, two with partial response, one with stable disease (>24 weeks), and one with progressive disease. The objective response rate was 71.4%. Progression-free survival ranged between 2 and 36 months (median 12 months), whereas overall survival ranged between 4 and 111 months (median 36 months). One patient experienced a grade 4 adverse event (neutropenia), which was conservatively manageable. Our study revealed a preferable objective response rate of Cmab-PTX for patients with high-grade SGC. Although the treatment sensitivity of SGC with high-grade histological types is usually poor, Cmab-PTX could be a promising treatment regimen for recurrent SGC.

1.
Lewis
AG
,
Tong
T
,
Maghami
E
.
Diagnosis and management of malignant salivary gland tumors of the parotid gland
.
Otolaryngol Clin North Am
.
2016
;
49
(
2
):
343
80
.
2.
Mueller
SK
,
Haderlein
M
,
Lettmaier
S
,
Agaimy
A
,
Haller
F
,
Hecht
M
et al
.
Targeted therapy, chemotherapy, immunotherapy and novel treatment options for different subtypes of salivary gland cancer
.
J Clin Med
.
2022
3
11
.
3.
Guazzo
E
,
Cooper
C
,
Wilkinson
L
,
Feng
S
,
King
B
,
Simpson
F
et al
.
Therapeutic implications of immune-profiling and EGFR expression in salivary gland carcinoma
.
Head Neck
.
2021
;
43
(
3
):
768
77
.
4.
Caballero
M
,
E Sosa
A
,
Tagliapietra
A
,
Grau
JJ
.
Metastatic adenoid cystic carcinoma of the salivary gland responding to cetuximab plus weekly paclitaxel after no response to weekly paclitaxel alone
.
Head Neck
.
2013
35
2
E52
4
.
5.
Yoshioka
Y
,
Toratani
S
,
Nakatao
H
,
Koizumi
K
,
Hayashido
Y
,
Okamoto
T
.
Weekly paclitaxel plus cetuximab reduces the lung metastasis of adenoid cystic carcinoma arising from the salivary gland
.
Oral Sci Int
.
2015
;
12
(
2
):
67
71
.
6.
Pirker
R
,
Pereira
JR
,
von Pawel
J
,
Krzakowski
M
,
Ramlau
R
,
Park
K
et al
.
EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study
.
Lancet Oncol
.
2012
;
13
(
1
):
33
42
.
7.
Hotte
SJ
,
Winquist
EW
,
Lamont
E
,
MacKenzie
M
,
Vokes
E
,
Chen
EX
et al
.
Imatinib mesylate in patients with adenoid cystic cancers of the salivary glands expressing c-kit: a princess margaret hospital phase II consortium study
.
J Clin Oncol
.
2005
;
23
(
3
):
585
90
.
8.
Pfeffer
MR
,
Talmi
Y
,
Catane
R
,
Symon
Z
,
Yosepovitch
A
,
Levitt
M
.
A phase II study of Imatinib for advanced adenoid cystic carcinoma of head and neck salivary glands
.
Oral Oncol
.
2007
;
43
(
1
):
33
6
.
9.
Ghosal
N
,
Mais
K
,
Shenjere
P
,
Julyan
P
,
Hastings
D
,
Ward
T
et al
.
Phase II study of cisplatin and imatinib in advanced salivary adenoid cystic carcinoma
.
Br J Oral Maxillofac Surg
.
2011
;
49
(
7
):
510
5
.
10.
Chau
NG
,
Hotte
SJ
,
Chen
EX
,
Chin
SF
,
Turner
S
,
Wang
L
et al
.
A phase II study of sunitinib in recurrent and/or metastatic Adenoid Cystic Carcinoma (ACC) of the salivary glands: current progress and challenges in evaluating molecularly targeted agents in ACC
.
Ann Oncol
.
2012
;
23
(
6
):
1562
70
.
11.
Keam
B
,
Kim
SB
,
Shin
SH
,
Cho
BC
,
Lee
KW
,
Kim
MK
et al
.
Phase 2 study of dovitinib in patients with metastatic or unresectable adenoid cystic carcinoma
.
Cancer
.
2015
;
121
(
15
):
2612
7
.
12.
Thomson
DJ
,
Silva
P
,
Denton
K
,
Bonington
S
,
Mak
SK
,
Swindell
R
et al
.
Phase II trial of sorafenib in advanced salivary adenoid cystic carcinoma of the head and neck
.
Head Neck
.
2015
;
37
(
2
):
182
7
.
13.
Ho
AL
,
Dunn
L
,
Sherman
EJ
,
Fury
MG
,
Baxi
SS
,
Chandramohan
R
et al
.
A phase II study of axitinib (AG-013736) in patients with incurable adenoid cystic carcinoma
.
Ann Oncol
.
2016
;
27
(
10
):
1902
8
.
14.
Dillon
PM
,
Petroni
GR
,
Horton
BJ
,
Moskaluk
CA
,
Fracasso
PM
,
Douvas
MG
et al
.
A phase II study of dovitinib in patients with recurrent or metastatic adenoid cystic carcinoma
.
Clin Cancer Res
.
2017
;
23
(
15
):
4138
45
.
15.
Tchekmedyian
V
,
Sherman
EJ
,
Dunn
L
,
Tran
C
,
Baxi
S
,
Katabi
N
et al
.
Phase II study of lenvatinib in patients with progressive, recurrent or metastatic adenoid cystic carcinoma
.
J Clin Oncol
.
2019
;
37
(
18
):
1529
37
.
16.
Locati
LD
,
Galbiati
D
,
Calareso
G
,
Alfieri
S
,
Singer
S
,
Cavalieri
S
et al
.
Patients with adenoid cystic carcinomas of the salivary glands treated with lenvatinib: activity and quality of life
.
Cancer
.
2020
;
126
(
9
):
1888
94
.
17.
Roskoski
R
Jr
.
The ErbB/HER family of protein-tyrosine kinases and cancer
.
Pharmacol Res
.
2014
;
79
:
34
74
.
18.
Min
HY
,
Lee
HY
.
Molecular targeted therapy for anticancer treatment
.
Exp Mol Med
.
2022
;
54
(
10
):
1670
94
.
19.
Haddad
R
,
Colevas
AD
,
Krane
JF
,
Cooper
D
,
Glisson
B
,
Amrein
PC
et al
.
Herceptin in patients with advanced or metastatic salivary gland carcinomas. A phase II study
.
Oral Oncol
.
2003
;
39
(
7
):
724
7
.
20.
Agulnik
M
,
Cohen
EW
,
Cohen
RB
,
Chen
EX
,
Vokes
EE
,
Hotte
SJ
et al
.
Phase II study of lapatinib in recurrent or metastatic epidermal growth factor receptor and/or erbB2 expressing adenoid cystic carcinoma and non adenoid cystic carcinoma malignant tumors of the salivary glands
.
J Clin Oncol
.
2007
;
25
(
25
):
3978
84
.
21.
Locati
LD
,
Bossi
P
,
Perrone
F
,
Potepan
P
,
Crippa
F
,
Mariani
L
et al
.
Cetuximab in recurrent and/or metastatic salivary gland carcinomas: a phase II study
.
Oral Oncol
.
2009
;
45
(
7
):
574
8
.
22.
Jakob
JA
,
Kies
MS
,
Glisson
BS
,
Kupferman
ME
,
Liu
DD
,
Lee
JJ
et al
.
Phase II study of gefitinib in patients with advanced salivary gland cancers
.
Head Neck
.
2015
;
37
(
5
):
644
9
.
23.
Kinoshita
I
,
Kano
S
,
Shimizu
Y
,
Kiyota
N
,
Tada
Y
,
Ijichi
K
et al
.
Abstract CT137: phase II study of trastuzumab and docetaxel therapy in patients with HER2-positive recurrent and/or metastatic salivary gland carcinoma
.
Cancer Res
.
2019
79
13_Suppl ment
CT137
37
.
24.
Takahashi
H
,
Tada
Y
,
Saotome
T
,
Akazawa
K
,
Ojiri
H
,
Fushimi
C
et al
.
Phase II trial of trastuzumab and docetaxel in patients with human epidermal growth factor receptor 2-positive salivary duct carcinoma
.
J Clin Oncol
.
2019
;
37
(
2
):
125
34
.
25.
Kurzrock
R
,
Bowles
DW
,
Kang
H
,
Meric-Bernstam
F
,
Hainsworth
J
,
Spigel
DR
et al
.
Targeted therapy for advanced salivary gland carcinoma based on molecular profiling: results from MyPathway, a phase IIa multiple basket study
.
Ann Oncol
.
2020
;
31
(
3
):
412
21
.
26.
Kawakita
D
,
Nagao
T
,
Takahashi
H
,
Kano
S
,
Honma
Y
,
Hirai
H
et al
.
Survival benefit of HER2-targeted or androgen deprivation therapy in salivary duct carcinoma
.
Ther Adv Med Oncol
.
2022
;
14
:
17588359221119538
.
27.
Nakano
T
,
Yasumatsu
R
,
Hashimoto
K
,
Kuga
R
,
Hongo
T
,
Yamamoto
H
et al
.
Retrospective study of cisplatin/carboplatin, 5-fluorouracil plus cetuximab (EXTREME) for advanced-stage salivary gland cancer
.
In Vivo
.
2022
;
36
(
2
):
979
84
.
28.
Uijen
MJM
,
Lassche
G
,
van Engen-van Grunsven
ACH
,
Driessen
CML
,
van Herpen
CML
.
Case series of docetaxel, trastuzumab, and pertuzumab (DTP) as first line anti-HER2 therapy and ado-trastuzumab emtansine (T-DM1) as second line for recurrent or metastatic HER2-positive salivary duct carcinoma
.
Oral Oncol
.
2022
;
125
:
105703
.
29.
Javaheripour
A
,
Saatloo
MV
,
Vahed
N
,
Gavgani
LF
,
Kouhsoltani
M
.
Evaluation of HER2/neu expression in different types of salivary gland tumors: a systematic review and meta-analysis
.
J Med Life
.
2022
;
15
(
5
):
595
600
.
30.
Demetri
GD
,
De Braud
F
,
Drilon
A
,
Siena
S
,
Patel
MR
,
Cho
BC
et al
.
Updated integrated analysis of the efficacy and safety of entrectinib in patients with NTRK fusion-positive Solid tumors
.
Clin Cancer Res
.
2022
;
28
(
7
):
1302
12
.
31.
Boon
E
,
van Boxtel
W
,
Buter
J
,
Baatenburg de Jong
RJ
,
van Es
RJJ
,
Bel
M
et al
.
Androgen deprivation therapy for androgen receptor-positive advanced salivary duct carcinoma: a nationwide case series of 35 patients in The Netherlands
.
Head Neck
.
2018
;
40
(
3
):
605
13
.
32.
Fushimi
C
,
Tada
Y
,
Takahashi
H
,
Nagao
T
,
Ojiri
H
,
Masubuchi
T
et al
.
A prospective phase II study of combined androgen blockade in patients with androgen receptor-positive metastatic or locally advanced unresectable salivary gland carcinoma
.
Ann Oncol
.
2018
;
29
(
4
):
979
84
.
33.
Viscuse
PV
,
Price
KA
,
Garcia
JJ
,
Schembri-Wismayer
DJ
,
Chintakuntlawar
AV
.
First line androgen deprivation therapy vs. Chemotherapy for patients with androgen receptor positive recurrent or metastatic salivary gland carcinoma-A retrospective study
.
Front Oncol
.
2019
;
9
:
701
.
34.
Locati
LD
,
Cavalieri
S
,
Bergamini
C
,
Resteghini
C
,
Colombo
E
,
Calareso
G
et al
.
Abiraterone acetate in patients with castration-resistant, androgen receptor–expressing salivary gland cancer: a phase II trial
.
J Clin Oncol
.
2021
;
39
(
36
):
4061
8
.
35.
Ho
AL
,
Foster
NR
,
Zoroufy
AJ
,
Campbell
JD
,
Worden
F
,
Price
K
et al
.
Phase II study of enzalutamide for patients with androgen receptor–positive salivary gland cancers (alliance A091404)
.
J Clin Oncol
.
2022
;
40
(
36
):
4240
9
.
36.
Liu
C
,
Yang
M
,
Zhang
D
,
Chen
M
,
Zhu
D
.
Clinical cancer immunotherapy: current progress and prospects
.
Front Immunol
.
2022
;
13
:
961805
.
37.
Linxweiler
M
,
Kuo
F
,
Katabi
N
,
Lee
M
,
Nadeem
Z
,
Dalin
MG
et al
.
The immune microenvironment and neoantigen landscape of aggressive salivary gland carcinomas differ by subtype
.
Clin Cancer Res
.
2020
;
26
(
12
):
2859
70
.
38.
Vermorken
JB
,
Mesia
R
,
Rivera
F
,
Remenar
E
,
Kawecki
A
,
Rottey
S
et al
.
Platinum-based chemotherapy plus cetuximab in head and neck cancer
.
N Engl J Med
.
2008
;
359
(
11
):
1116
27
.
39.
Flynn
MB
,
Maguire
S
,
Martinez
S
,
Tesmer
T
.
Primary squamous cell carcinoma of the parotid gland: the importance of correct histological diagnosis
.
Ann Surg Oncol
.
1999
;
6
(
8
):
768
70
.
40.
Gilbert
J
,
Li
Y
,
Pinto
HA
,
Jennings
T
,
Kies
MS
,
Silverman
P
et al
.
Phase II trial of taxol in salivary gland malignancies (E1394): a trial of the Eastern Cooperative Oncology Group
.
Head Neck
.
2006
;
28
(
3
):
197
204
.
41.
Hill
ME
,
Constenla
DO
,
A'Hern
RP
,
Henk
JM
,
Rhys-Evans
P
,
Breach
N
et al
.
Cisplatin and 5-fluorouracil for symptom control in advanced salivary adenoid cystic carcinoma
.
Oral Oncol
.
1997
;
33
(
4
):
275
8
.
42.
Rubió-Casadevall
J
,
Cirauqui Cirauqui
B
,
Martinez Trufero
J
,
Plana Serrahima
M
,
García Castaño
A
,
Carral Maseda
A
et al
.
TTCC-2019-02: real-world evidence of first-line cetuximab plus paclitaxel in recurrent or metastatic squamous cell carcinoma of the head and neck
.
Front Oncol
.
2023
;
13
:
1226939
.
43.
Morash
M
,
Mitchell
H
,
Beltran
H
,
Elemento
O
,
Pathak
J
.
The role of next-generation sequencing in precision medicine: a review of outcomes in oncology
.
J Pers Med
.
2018
;
8
(
3
):
30
.
44.
Imamura
Y
,
Kiyota
N
,
Tahara
M
,
Hanai
N
,
Asakage
T
,
Matsuura
K
et al
.
Systemic therapy for salivary gland malignancy: current status and future perspectives
.
Jpn J Clin Oncol
.
2022
;
52
(
4
):
293
302
.
45.
Szewczyk
M
,
Marszalek
A
,
Sygut
J
,
Golusinski
P
,
Golusinski
W
.
Prognostic markers in salivary gland cancer and their impact on survival
.
Head Neck
.
2019
;
41
(
9
):
3338
47
.
46.
Burman
B
,
Sherman
EJ
,
Dunn
L
,
Fetten
JV
,
Michel
LS
,
Morris
LGT
et al
.
A phase II trial cohort of nivolumab plus ipilimumab in Patients (Pts) with Recurrent/Metastatic Salivary Gland Cancers (R/M SGCs)
.
J Clin Oncol
.
2021
39
15_Suppl l
6002
2
.
47.
Sato
R
,
Kumai
T
,
Ishida
Y
,
Yuasa
R
,
Kubota
A
,
Wakisaka
R
et al
.
The efficacy of PD-1 inhibitors in patients with salivary gland carcinoma: a retrospective observational study
.
Laryngoscope Investig Otolaryngol
.
2022
;
7
(
6
):
1808
13
.
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