First-line cisplatin, docetaxel, and cetuximab for patients with recurrent or metastatic head and neck cancer: A multicenter cohort study

Table 1 Clinicopathological characteristics

Characteristics	Number of patients (%)
Total	24
Median age (range), yr	58 (36-77)
Sex
Male	15 (62.5)
Female	9 (37.5)
ECOG at TPEx treatment initiation
0-1	22 (91.7)
2	2 (8.3)
Smoking history
Never	6 (25)
Current or former	13 (54.2)
NS	5 (20.8)
Alcohol consumption
Occasional or regular	8 (33.3)
None	7 (29.2)
NS	9 (37.5)
Primary tumor site
Larynx	7 (29.2)
Oropharynx	6 (25)
Oral cavity	5 (20.8)
Hypopharynx	1 (4.2)
Other	5 (20.8)
Previous treatment
Concomitant chemoradiotherapy only	8 (33.3)
Surgery only	5 (20.8)
Surgery + concomitant chemoradiotherapy	5 (20.8)
Surgery + radiotherapy	3 (12.5)
Radiotherapy only	1 (4.2)
No	2 (8.3)
Extent of disease at TPEx treatment initiation
Locoregional recurrence only	14 (58.3)
Locoregional recurrence + distant metastasis	5 (20.8)
Metastatic disease	5 (20.8)
Time from initial diagnosis to recurrence(Median, IQR), mo	16.2 (5.4-37.5)
Metastatic or unresectable disease at diagnosis	11 (45.8)

NS: Not specified; ECOG: Eastern Cooperative Oncology Group; HPV: Human papilloma virus; IQR: Interquartile range.

Table 2 Summary of treatment response

	TPEx (n = 24)
Type of response, n (%)
Complete	3 (12.5)
Partial	12 (50)
Stable disease	6 (25)
Progression	1 (4.2)
Nonassessable	2 (8.3)
Objective response rate - % of patients (95%CI)1	62.5
Disease-control rate - % of patients (95%CI)2	87.5
Time to response – mo3
Median (95%CI)	2.4 (1.3-3.5)
Duration of response – mo4
Median (95%CI)	5.1 (3.0-7.2)

¹An objective response was considered to be a confirmed complete or partial response, as assessed by the investigator.

²The disease-control rate was calculated considering patients with a confirmed complete response, partial response, or stable disease as assessed by the investigator.

³The time to response was calculated with the use of the Kaplan-Meier method from the date of TPEx initiation to the date of the first documented partial or complete response.

⁴The duration of response was calculated with the use of the Kaplan-Meier method from the date of the first documented response until the date of documented disease progression, death, or the last response assessment in the absence of disease progression.

CI: Confidence interval.

Table 3 Univariate prognostic factor analyses for TPEx progression-free survival

Variable	HR (95%CI)	P value	Median PFS (95%CI)
ECOG(0 vs 1-2)	0.91 (0.30-2.80)	0.87	6.9 mo (5.1-8.8) vs 6.8 mo (4.7-8.9)
Primary tumor site (Hypo/oropharyngeal vs Others)	0.15 (0.02-1.17)	0.04	22 mo (19.9-25.1) vs 6.7 mo (4.7-8.9)
Response (Responders vs Nonresponders)	0.34 (0.12–0.97)	0.04	8.5 mo (5.5-11.5) vs 4.5 mo (2.5-6.5)
Extent of disease at TPEx initiation (Locoregionally advanced vs Metastatic)	0.95 (0.33-2.85)	0.95	6.9 mo (4.2-9.7) vs 6.8 mo (5.6-7.8)
Relapse-free survival of the primary treatment (≤ 24 vs > 24 mo)1	0.37 (0.11-1.21)	0.09	6.1 mo (3.6-8.6) vs 8.5 mo (4.5-12.5)
Previous treatment2(Multimodality vs Unimodality)	0.44 (0.14–1.41)	0.17	7.5 mo (6.3-8.7) vs 6.1 mo (2.7-9.4)
Treatment interruption, discontinuation, or dose reduction (Yes vs No)	1.15 (0.39-3.41)	0.80	6.9 mo (6.4-7.4) vs 6.8 mo (5.0-8.5)
Adverse events (Grade 1-2 vs 3-4)	0.74 (0.23-2.44)	0.62	6.9 mo (5.2-8.6) vs 6.7 mo (0.3-13.9)

¹Time from primary definitive treatment to advanced disease and first-line TPEx initiation.

²Treatment received as primary intention.

Unimodality included surgery or radiotherapy only. Multimodality included surgery and/or radiotherapy +/- chemotherapy. ECOG: Eastern Cooperative Oncology Group; CI: Confidence interval.

Table 4 Adverse events of any cause during TPEx treatment

Event, n (%)	TPEx (n = 24)
	Any grade	Grade 3	Grade 4
Any treatment-related adverse event1	18 (75)	6 (25)	0
Hematological
Febrile neutropenia	3 (12.5)	3 (12.5)	0
Anemia	3 (12.5)	0
Hyponatremia and/or hypokalemia	3 (12.5)	2 (8.3)	0
Hypomagnesemia	2 (8.3)	1 (4.2)	0
Thrombocytopenia	1 (4.2)	0	0
Nonhematological
Acne-like rash	8 (33.3)	0	0
Nausea - vomiting	4 (16.7)	1 (4.2)	0
Asthenia	4 (16.7)	1 (4.2)	0
Diarrhea	2 (8.3)	0	0
Renal failure	1 (4.2)	1 (4.2)	0
Hypersensitivity	1 (4.2)	0
Oral mucositis	1 (4.2)	0	0
Any serious adverse event2	-	5 (20.8)	0
Treatment-related death	0	-	-
Event leading to interruption of any treatment component3	3 (12.5)	-	-
Chemotherapy	2 (8.3)	-	-
Cetuximab	1 (4.2)	-	-
Event leading to discontinuation of any treatment component3	2 (8.3)	-	-
Chemotherapy	2 (8.3)	-	-
Cetuximab	0
Event leading to dose reduction	2 (8.3)	-	-

¹The investigators determined whether adverse events were related to the treatment.

²Adverse events that lead to hospitalization.

³This category includes patients who experienced cisplatin, docetaxel, or cetuximab treatment interruption or discontinuation because of an adverse event at any time and patients who experienced cetuximab maintenance therapy interruption or discontinuation for an adverse event after completing the chemotherapy cycles.

Events were attributed to the specific treatment by the investigator.

Table 5 Selected studies that assessed first-line TPEx schema in patients with recurrent or metastatic head and neck cancer

Ref.	Study type	n	ORR (%)	PFS (mo)	OS (mo)	Grade 3, adverse events (%)	Grade 4, adverse events (%)
Guigay et al[19]	Phase 2	541	57.6	6.0	14.5	73	33
Guigay et al[14]	Phase 2	54	44.4	6.2	14	93	22
Bossi et al[15]	Phase 21	201	51.7	7.0	11	73	33
Even et al[21]	Retrospective	30	87	6.0	13.6	17	10
Fuchs et al[22]	Retrospective	38	50	6.3	10.8	100

¹This trial used paclitaxel.

ORR: Overall response rate; PFS: Progression-free survival; OS: Overall survival.