Study of Nivolumab in Unresectable Advanced or Recurrent Esophageal Cancer

• Sponsor: Ono Pharmaceutical Co. Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02569242
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 419
• Locations: 89
• Arms: 2
• Actual Duration (Months): 58.3
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of study is to evaluate the efficacy and safety of Nivolumab in unresectable advanced or recurrent esophageal cancer patients who have failed in standard chemotherapies.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer	Drug: Nivolumab; Drug: Docetaxel/Paclitaxel	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 419 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: ONO-4538 Phase III Study A Multicenter, Randomized, Open-label Study in Patients With Esophageal Cancer Refractory or Intolerant to Combination Therapy With Fluoropyrimidine and Platinum-based Drugs
• Actual Study Start Date: Dec 14, 2015
• Actual Primary Completion Date: Oct 23, 2020
• Actual Study Completion Date: Oct 23, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nivolumab Arm Nivolumab 240 mg/body solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends	Drug: Nivolumab
Active Comparator: Active Comparator Arm （Docetaxel/Paclitaxel） Docetaxel: Intravenously administered at a dose of 75 mg/m2 every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends OR Paclitaxel: Intravenously administered at a dose of 100 mg/m2 weekly for 6 weeks followed by 2-week drug holiday until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends	Drug: Docetaxel/Paclitaxel

Outcome Measures

Primary Outcome Measures

1. Overall Survival [("Date of death from any cause" - "Date of randomization" + 1) / 30.4375. For subjects lost to follow-up and subjects who are alive at the time of data cutoff date, data will be censored at the time the subject was last confirmed to be alive.]

Secondary Outcome Measures

1. Progression-free Survival [("Earlier date on which either the overall response was assessed as PD or the subject died of any cause" - "Date of randomization" + 1) / 30.4375.]

   Please refer to the protocol, overall response and best overall response will be determined solely by imaging assessment according to the RECIST Guideline Version 1.1, and will not take into account any clinical/symptomatic progression. Evaluable imaging data will be overall response without an overall response of "Not Evaluable (NE)."

2. Duration of Response [("Earlier date on which either the overall response was assessed as PD for the first time after confirmed response or the subject died of any cause" - "Date of first assessment of confirmed CR or PR" + 1) / 30.4375.]

   Please refer to the protocol, overall response and best overall response will be determined solely by imaging assessment according to the RECIST Guideline Version 1.1, and will not take into account any clinical/symptomatic progression. Evaluable imaging data will be overall response without an overall response of "Not Evaluable (NE)."

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men & women ≥20 years of age

• Histologically confirmed unresectable advanced or recurrent esophageal cancer

• Refractory to or intolerant of standard therapy

• ECOG Performance Status score 0 or 1

• A life expectancy of at least 3 months

Exclusion Criteria:

• Current or past history of severe hypersensitivity to any other antibody products

• Patients with multiple primary cancers

• Patients with any metastasis in the brain or meninx that is symptomatic or requires treatment

• Patients with active, known or suspected autoimmune disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Banner MD Anderson Cancer Center	Gilbert	Arizona	United States	85234
2	Georgetown University Med Ctr	Washington	District of Columbia	United States	20007
3	Orlando Health, Inc	Orlando	Florida	United States	32806
4	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
5	Duke Cancer Institute	Durham	North Carolina	United States	27710
6	Vanderbilt-Ingram Cancer Ctr	Nashville	Tennessee	United States	37232
7	The University Of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
8	Odense University Hospital	Odense C		Denmark	5000
9	RWTH Aachen University	Aachen		Germany	52057
10	Charite Campus Virchow Klinikum	Berlin		Germany	D-13353
11	University Hospital Heidelberg	Heidelberg		Germany	69120
12	Universitatsklinikum Jena, Innere Medizin II	Jena		Germany	07747
13	MVZ Mitte	Leipzig		Germany	04103
14	University Of Mainz Medical Center	Mainz		Germany	55131
15	Klinikum reechts der Isar, Technical University Munchen	Munich		Germany	81675
16	HPG23	Bergamo		Italy	24127
17	Fondazione Irccs Istituto Nazionale Tumori	Milan		Italy	20133
18	Irccs Istituto Oncologico Veneto Iov	Padova		Italy	35128
19	Aichi Clinical Site	Nagoya	Aichi	Japan	464-8681
20	Aichi Clinical Site	Nagoya	Aichi	Japan	466-8560
21	Aomori Clinical Site	Hirosaki	Aomori	Japan	036-8563
22	Chiba Clinical Site	Kashiwa	Chiba	Japan	277-8577
23	Ehime Clinical Site	Matsuyama	Ehime	Japan	791-0288
24	Hokkaido Clinical Site	Sapporo	Hokkaido	Japan	003-0027
25	Hokkaido Clinical Site	Sapporo	Hokkaido	Japan	060-8648
26	Hyogo Clinical Site	Akashi	Hyogo	Japan	673-0021
27	Hyogo Clinical Site	Kobe	Hyogo	Japan	650-0047
28	Kanagawa Clinical Site	Isehara	Kanagawa	Japan	259-1193
29	Kanagawa Clinical Site	Kawasaki	Kanagawa	Japan	216-0015
30	Kanagawa Clinical Site	Yokohama	Kanagawa	Japan	236-0004
31	Kanagawa Clinical Site	Yokohama	Kanagawa	Japan	241-8515
32	Mie Clinical Site	Tsu	Mie	Japan	514-8507
33	Miyagi Clinical Site	Sendai	Miyagi	Japan	980-8574
34	Nagano Clinical Site	Saku	Nagano	Japan	385-0051
35	Niigata Clinical Site	Nigatake	Niigata	Japan	951-8520
36	Osaka Clinical Site	Osakasayama	Osaka	Japan	589-8511
37	Osaka Clinical Site	Suita	Osaka	Japan	565-0871
38	Osaka Clinical Site	Takatsuki	Osaka	Japan	569-0801
39	Saitama Clinical Site	Hidaka	Saitama	Japan	350-1298
40	Saitama Clinical Site	Kita-Adachi County	Saitama	Japan	362-0806
41	Shizuoka Clinical Site	Suntou County	Shizuoka	Japan	411-8777
42	Tochigi Clinical Site	Shimotsuke	Tochigi	Japan	329-0431
43	Tokyo Clinical Site	Bunkyo-ku	Tokyo	Japan	113-0021
44	Tokyo Clinical Site	Chuo-ku	Tokyo	Japan	104-0045
45	Tokyo Clinical Site	Chuo-ku	Tokyo	Japan	104-8560
46	Tokyo Clinical Site	Koto-ku	Tokyo	Japan	135-8550
47	Tokyo Clinical Site	Meguro-ku	Tokyo	Japan	152-8902
48	Tokyo Clinical Site	Minato-ku	Tokyo	Japan	105-8470
49	Tokyo Clinical Site	Shinagawa-ku	Tokyo	Japan	142-8666
50	Tokyo Clinical Site	Shinjuku-ku	Tokyo	Japan	160-8582
51	Tokyo Clinical Site	Shinjuku-ku	Tokyo	Japan	162-8666
52	Akita Clinical Site	Akita		Japan	010-8543
53	Chiba Clinical Site	Chiba		Japan	260-0801
54	Chiba Clinical Site	Chiba		Japan	260-8677
55	Fukuoka Clinical Site	Fukuoka		Japan	812-8582
56	Fukushima Clinical Site	Fukushima		Japan	960-1295
57	Hiroshima Clinical Site	Hiroshima		Japan	734-8551
58	Kagoshima Clinical Site	Kagoshima		Japan	890-8520
59	Kumamoto Clinical Site	Kumamoto		Japan	860-8556
60	Kyoto Clinical Site	Kyoto		Japan	602-8566
61	Kyoto Clinical Site	Kyoto		Japan	606-8507
62	Niigata Clinical Site	Niigata		Japan	951-8566
63	Osaka Clinical Site	Osaka		Japan	537-8511
64	Shizuoka Clinical Site	Shizuoka		Japan	420-8527
65	Busan Clinical Site	Busan		Korea, Republic of	49241
66	Daegu Clinical Site	Daegu		Korea, Republic of	41404
67	Daegu Clinical Site	Daegu		Korea, Republic of	41931
68	Daejeon Clinical Site	Daejeon		Korea, Republic of	35015
69	Gyeonggi-do Clinical Site	Gyeonggi-do		Korea, Republic of	13620
70	Hwasun-Gun Clinical Site	Hwasun-Gun		Korea, Republic of	58128
71	Seoul Clinical Site	Seoul		Korea, Republic of	03080
72	Seoul Clinical Site	Seoul		Korea, Republic of	03722
73	Seoul Clinical Site	Seoul		Korea, Republic of	05505
74	Seoul Clinical Site	Seoul		Korea, Republic of	06351
75	Seoul Clinical Site	Seoul		Korea, Republic of	06591
76	Ulsan Clinical Site	Ulsan		Korea, Republic of	44033
77	Changhua Clinical Site	Changhua		Taiwan	500
78	Chiayi Clinical Site	Chiayi		Taiwan	61363
79	Kaohsiung Clinical Site	Kaohsiung		Taiwan	807
80	Kaohsiung Clinical Site	Kaohsiung		Taiwan	82445
81	Kaohsiung Clinical Site	Kaohsiung		Taiwan	83301
82	Keelung Clinical Site	Keelung		Taiwan	20445
83	Taichung Clinical Site	Taichung		Taiwan	40447
84	Tainan Clinical Site	Tainan		Taiwan	704
85	Taipei Clinical Site	Taipei		Taiwan	10048
86	Taipei Clinical Site	Taipei		Taiwan	11217
87	Taoyuan Clinical Site	Taoyuan		Taiwan	333
88	Velindre Cancer Centre	Cardiff	Cardiganshire	United Kingdom	CF142TL
89	The Beatson West Of Scotland Cancer Centre	Glasgow	Lanarkshire	United Kingdom	G12 0YN

Sponsors and Collaborators

• Ono Pharmaceutical Co. Ltd
• Bristol-Myers Squibb

Investigators

• Study Director: Ono Pharmaceutical Co., Ltd. Ono Pharmaceutical Co., Ltd., Ono Pharmaceutical Co. Ltd

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 7, 2017

More Information

Publications

None provided.

• Responsible Party: Ono Pharmaceutical Co. Ltd
• ClinicalTrials.gov Identifier: NCT02569242
• Other Study ID Numbers: ONO-4538-24/CA209-473
• First Posted: Oct 6, 2015
• Last Update Posted: Jul 6, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Esophageal Neoplasms; Paclitaxel; Docetaxel; Nivolumab

Study Results

Participant Flow

Arm/Group Title	Nivolumab Arm	Active Comparator Arm （Docetaxel/Paclitaxel）
Arm/Group Description	Nivolumab 240 mg/body solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends	Docetaxel: Intravenously administered at a dose of 75 mg/m2 every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends OR Paclitaxel: Intravenously administered at a dose of 100 mg/m2 weekly for 6 weeks followed by 2-week drug holiday until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
Period Title: Overall Study
STARTED	210	209
COMPLETED	209	208
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Nivolumab Arm	Active Comparator Arm （Docetaxel/Paclitaxel）	Total
Arm/Group Description	Nivolumab 240 mg/body solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends	Docetaxel: Intravenously administered at a dose of 75 mg/m2 every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends OR Paclitaxel: Intravenously administered at a dose of 100 mg/m2 weekly for 6 weeks followed by 2-week drug holiday until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends	Total of all reporting groups
Overall Participants	210	209	419
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	112 53.3%	85 40.7%	197 47%
>=65 years	98 46.7%	124 59.3%	222 53%
Age (years) [Mean (Inter-Quartile Range) ]
Mean (Inter-Quartile Range) [years]	64	67	65
Sex: Female, Male (Count of Participants)
Female	31 14.8%	24 11.5%	55 13.1%
Male	179 85.2%	185 88.5%	364 86.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	201 95.7%	200 95.7%	401 95.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	9 4.3%	9 4.3%	18 4.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian	201 95.7%	200 95.7%	401 95.7%
White	9 4.3%	9 4.3%	18 4.3%
ECOG performance status (Count of Participants)
0	101 48.1%	107 51.2%	208 49.6%
1	109 51.9%	102 48.8%	211 50.4%
Disease stage : TNM classification (Count of Participants)
II - III	8 3.8%	13 6.2%	21 5%
IV	94 44.8%	100 47.8%	194 46.3%
unknown	5 2.4%	7 3.3%	12 2.9%
Previous therapies (Count of Participants)
Surgery	111 52.9%	94 45%	205 48.9%
Radiothrapy	153 72.9%	142 67.9%	295 70.4%
Systemic anticancer therapy	210 100%	208 99.5%	418 99.8%
Number of organs of metastases (Count of Participants)
<=1	89 42.4%	91 43.5%	180 43%
>=2	121 57.6%	118 56.5%	239 57%
Site of metastases (Count of Participants)
Lymph node	159 75.7%	163 78%	322 76.8%
Liver	57 27.1%	54 25.8%	111 26.5%
Lung	98 46.7%	92 44%	190 45.3%
Bone	23 11%	25 12%	48 11.5%
PD-L1 expression (Count of Participants)
<1%	109 51.9%	107 51.2%	216 51.6%
>=1%	101 48.1%	102 48.8%	203 48.4%
<5%	136 64.8%	137 65.6%	273 65.2%
>=5%	74 35.2%	72 34.4%	146 34.8%
<10%	146 69.5%	152 72.7%	298 71.1%
>=10%	64 30.5%	57 27.3%	121 28.9%
History of smoking (Count of Participants)
Never	30 14.3%	32 15.3%	62 14.8%
Former	159 75.7%	147 70.3%	306 73%
Current	21 10%	30 14.4%	51 12.2%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Time Frame	("Date of death from any cause" - "Date of randomization" + 1) / 30.4375. For subjects lost to follow-up and subjects who are alive at the time of data cutoff date, data will be censored at the time the subject was last confirmed to be alive.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nivolumab Arm	Active Comparator Arm （Docetaxel/Paclitaxel）
Arm/Group Description	Nivolumab 240 mg/body solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends	Docetaxel: Intravenously administered at a dose of 75 mg/m2 every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends OR Paclitaxel: Intravenously administered at a dose of 100 mg/m2 weekly for 6 weeks followed by 2-week drug holiday until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
Measure Participants	210	209
Median (95% Confidence Interval) [months]	10.9	8.4

2. Secondary Outcome

Title	Progression-free Survival
Description	Please refer to the protocol, overall response and best overall response will be determined solely by imaging assessment according to the RECIST Guideline Version 1.1, and will not take into account any clinical/symptomatic progression. Evaluable imaging data will be overall response without an overall response of "Not Evaluable (NE)."
Time Frame	("Earlier date on which either the overall response was assessed as PD or the subject died of any cause" - "Date of randomization" + 1) / 30.4375.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nivolumab Arm	Active Comparator Arm （Docetaxel/Paclitaxel）
Arm/Group Description	Nivolumab 240 mg/body solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends	Docetaxel: Intravenously administered at a dose of 75 mg/m2 every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends OR Paclitaxel: Intravenously administered at a dose of 100 mg/m2 weekly for 6 weeks followed by 2-week drug holiday until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
Measure Participants	210	209
Median (95% Confidence Interval) [months]	1.7	3.4

3. Secondary Outcome

Title	Duration of Response
Description	Please refer to the protocol, overall response and best overall response will be determined solely by imaging assessment according to the RECIST Guideline Version 1.1, and will not take into account any clinical/symptomatic progression. Evaluable imaging data will be overall response without an overall response of "Not Evaluable (NE)."
Time Frame	("Earlier date on which either the overall response was assessed as PD for the first time after confirmed response or the subject died of any cause" - "Date of first assessment of confirmed CR or PR" + 1) / 30.4375.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nivolumab Arm	Active Comparator Arm （Docetaxel/Paclitaxel）
Arm/Group Description	Nivolumab 240 mg/body solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends	Docetaxel: Intravenously administered at a dose of 75 mg/m2 every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends OR Paclitaxel: Intravenously administered at a dose of 100 mg/m2 weekly for 6 weeks followed by 2-week drug holiday until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
Measure Participants	210	209
Median (95% Confidence Interval) [months]	6.9	3.9

Adverse Events

Time Frame	Monitoring for any AEs will be continued until 28 days after the end of the treatment phase. In subjects who, at the time of initiation of the follow-up investigation, have any AE for which a causal relationship to the investigational product cannot be ruled out or which led to discontinuation, investigation of the AE will be continued until the event is judged not to require further follow-up. SAEs are to be collected during the treatment period and for 100 days following the last dose.
Adverse Event Reporting Description	For all-cause mortality, the number of adverse events reported as Grade 5 was extracted.
Arm/Group Title	Nivolumab Arm		Active Comparator Arm （Docetaxel/Paclitaxel）
Arm/Group Description	Nivolumab 240 mg/body solution intravenously every 2 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends		Docetaxel: Intravenously administered at a dose of 75 mg/m2 every 3 weeks until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends OR Paclitaxel: Intravenously administered at a dose of 100 mg/m2 weekly for 6 weeks followed by 2-week drug holiday until documented disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends
All Cause Mortality
	Nivolumab Arm		Active Comparator Arm （Docetaxel/Paclitaxel）
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/209 (3.3%)		5/208 (2.4%)
Serious Adverse Events
	Nivolumab Arm		Active Comparator Arm （Docetaxel/Paclitaxel）
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	68/209 (32.5%)		77/208 (37%)
Blood and lymphatic system disorders
Anemia	2/209 (1%)		0/208 (0%)
Febrile neutropenia	0/209 (0%)		16/208 (7.7%)
Pancytopenia	0/209 (0%)		1/208 (0.5%)
Bone marrow failure	0/209 (0%)		1/208 (0.5%)
Cardiac disorders
Angina pectoris	1/209 (0.5%)		0/208 (0%)
Cardiac failure	0/209 (0%)		1/208 (0.5%)
Pericarditis	0/209 (0%)		1/208 (0.5%)
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula	1/209 (0.5%)		0/208 (0%)
Endocrine disorders
Hyperthyroidism	1/209 (0.5%)		0/208 (0%)
Hypopituitarism	1/209 (0.5%)		0/208 (0%)
Inappropriate antidiuretic hormone secretion	1/209 (0.5%)		0/208 (0%)
Adrenocorticotropic hormone deficiency	1/209 (0.5%)		0/208 (0%)
Gastrointestinal disorders
Abdominal pain	1/209 (0.5%)		2/208 (1%)
Colitis	1/209 (0.5%)		0/208 (0%)
Diarrhoea	1/209 (0.5%)		2/208 (1%)
Duodenitis	1/209 (0.5%)		0/208 (0%)
Dysphagia	2/209 (1%)		2/208 (1%)
Gastrointestinal haemorrhage	1/209 (0.5%)		0/208 (0%)
Ileus	1/209 (0.5%)		1/208 (0.5%)
Intestinal obstruction	1/209 (0.5%)		1/208 (0.5%)
Nausea	0/209 (0%)		2/208 (1%)
Upper gastrointestinal haemorrhage	0/209 (0%)		1/208 (0.5%)
Vomiting	0/209 (0%)		2/208 (1%)
Gastric fistula	1/209 (0.5%)		0/208 (0%)
Aorto-oesophageal fistula	1/209 (0.5%)		0/208 (0%)
General disorders
Asthenia	0/209 (0%)		1/208 (0.5%)
Fatigue	1/209 (0.5%)		1/208 (0.5%)
Malaise	1/209 (0.5%)		1/208 (0.5%)
Pyrexia	6/209 (2.9%)		1/208 (0.5%)
Sudden death	1/209 (0.5%)		1/208 (0.5%)
Disease progression	0/209 (0%)		1/208 (0.5%)
Stenosis	0/209 (0%)		1/208 (0.5%)
Hepatobiliary disorders
Cholecystitis	1/209 (0.5%)		0/208 (0%)
Hepatic function abnormal	1/209 (0.5%)		0/208 (0%)
Bile duct obstruction	1/209 (0.5%)		0/208 (0%)
Immune system disorders
Anaphylactic shock	1/209 (0.5%)		0/208 (0%)
Drug hypersensitivity	1/209 (0.5%)		0/208 (0%)
Infections and infestations
Appendicitis	1/209 (0.5%)		0/208 (0%)
Bacteraemia	2/209 (1%)		0/208 (0%)
Bronchitis	1/209 (0.5%)		0/208 (0%)
Infection	1/209 (0.5%)		2/208 (1%)
Mediastinitis	1/209 (0.5%)		0/208 (0%)
Pneumonia	10/209 (4.8%)		13/208 (6.3%)
Postoperative wound infection	0/209 (0%)		1/208 (0.5%)
Sepsis	0/209 (0%)		2/208 (1%)
Septic shock	0/209 (0%)		1/208 (0.5%)
Upper respiratory tract infection	1/209 (0.5%)		0/208 (0%)
Urinary tract infection	2/209 (1%)		0/208 (0%)
Anal abscess	0/209 (0%)		1/208 (0.5%)
Muscle abscess	1/209 (0.5%)		0/208 (0%)
Abscess neck	0/209 (0%)		1/208 (0.5%)
Abdominal infection	1/209 (0.5%)		0/208 (0%)
Intervertebral discitis	1/209 (0.5%)		0/208 (0%)
Pneumonia bacterial	1/209 (0.5%)		1/208 (0.5%)
Lung infection	1/209 (0.5%)		5/208 (2.4%)
Infectious pleural effusion	0/209 (0%)		2/208 (1%)
Spinal cord abscess	0/209 (0%)		1/208 (0.5%)
Injury, poisoning and procedural complications
Radiation pneumonitis	1/209 (0.5%)		0/208 (0%)
Stoma site extravasation	0/209 (0%)		1/208 (0.5%)
Investigations
Blood creatine phosphokinase increased	1/209 (0.5%)		0/208 (0%)
Blood creatinine increased	1/209 (0.5%)		0/208 (0%)
Neutrophil count decreased	0/209 (0%)		3/208 (1.4%)
Liver function test increased	1/209 (0.5%)		0/208 (0%)
Metabolism and nutrition disorders
Cachexia	1/209 (0.5%)		1/208 (0.5%)
Dehydration	2/209 (1%)		1/208 (0.5%)
Hypercalcaemia	4/209 (1.9%)		1/208 (0.5%)
Hypoglycaemia	2/209 (1%)		0/208 (0%)
Hyponatraemia	1/209 (0.5%)		1/208 (0.5%)
Decreased appetite	3/209 (1.4%)		6/208 (2.9%)
Musculoskeletal and connective tissue disorders
Fistula	0/209 (0%)		1/208 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lymph nodes	1/209 (0.5%)		0/208 (0%)
Skin cancer	0/209 (0%)		1/208 (0.5%)
Tumour haemorrhage	3/209 (1.4%)		1/208 (0.5%)
Malignant neoplasm progression	2/209 (1%)		0/208 (0%)
Lymphangiosis carcinomatosa	1/209 (0.5%)		0/208 (0%)
Cancer pain	1/209 (0.5%)		0/208 (0%)
Renal and urinary disorders
Acute kidney injury	1/209 (0.5%)		0/208 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/209 (1.4%)		1/208 (0.5%)
Interstitial lung disease	4/209 (1.9%)		3/208 (1.4%)
Pleural effusion	1/209 (0.5%)		3/208 (1.4%)
Pleurisy	0/209 (0%)		1/208 (0.5%)
Pneumonia aspiration	3/209 (1.4%)		2/208 (1%)
Pneumonitis	3/209 (1.4%)		3/208 (1.4%)
Pneumothorax	1/209 (0.5%)		3/208 (1.4%)
Pneumothorax spontaneous	1/209 (0.5%)		0/208 (0%)
Pulmonary embolism	1/209 (0.5%)		0/208 (0%)
Respiratory failure	1/209 (0.5%)		0/208 (0%)
Oesophagobronchial fistula	2/209 (1%)		0/208 (0%)
Tracheal fistula	1/209 (0.5%)		0/208 (0%)
Skin and subcutaneous tissue disorders
Skin ulcer	0/209 (0%)		1/208 (0.5%)
Stevens-Johnson syndrome	1/209 (0.5%)		0/208 (0%)
Surgical and medical procedures
Jejunostomy	1/209 (0.5%)		0/208 (0%)
Vascular disorders
Hypotension	0/209 (0%)		1/208 (0.5%)
Venous thrombosis	0/209 (0%)		1/208 (0.5%)
Embolism	0/209 (0%)		1/208 (0.5%)
Other (Not Including Serious) Adverse Events
	Nivolumab Arm		Active Comparator Arm （Docetaxel/Paclitaxel）
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	185/209 (88.5%)		204/208 (98.1%)
Blood and lymphatic system disorders
Anaemia	24/209 (11.5%)		61/208 (29.3%)
Leukopenia	0/209 (0%)		18/208 (8.7%)
Neutropenia	1/209 (0.5%)		40/208 (19.2%)
Endocrine disorders
Hypothyroidism	21/209 (10%)		3/208 (1.4%)
Gastrointestinal disorders
Abdominal pain	12/209 (5.7%)		8/208 (3.8%)
Constipation	35/209 (16.7%)		40/208 (19.2%)
Diarrhoea	36/209 (17.2%)		34/208 (16.3%)
Dysphagia	13/209 (6.2%)		3/208 (1.4%)
Nausea	23/209 (11%)		40/208 (19.2%)
Stomatitis	7/209 (3.3%)		26/208 (12.5%)
Vomiting	12/209 (5.7%)		17/208 (8.2%)
General disorders
Chest pain	13/209 (6.2%)		4/208 (1.9%)
Fatigue	19/209 (9.1%)		52/208 (25%)
Malaise	12/209 (5.7%)		49/208 (23.6%)
Pyrexia	29/209 (13.9%)		38/208 (18.3%)
Infections and infestations
Nasopharyngitis	13/209 (6.2%)		9/208 (4.3%)
Upper respiratory tract infection	15/209 (7.2%)		13/208 (6.3%)
Investigations
Alanine aminotransferase increased	11/209 (5.3%)		7/208 (3.4%)
Aspartate aminotransferase increased	13/209 (6.2%)		7/208 (3.4%)
Lymphocyte count decreased	5/209 (2.4%)		21/208 (10.1%)
Neutrophil count decreased	3/209 (1.4%)		76/208 (36.5%)
Weight decreased	11/209 (5.3%)		11/208 (5.3%)
White blood cell count decreased	2/209 (1%)		72/208 (34.6%)
Metabolism and nutrition disorders
Decreased appetite	40/209 (19.1%)		68/208 (32.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	10/209 (4.8%)		25/208 (12%)
Myalgia	6/209 (2.9%)		22/208 (10.6%)
Nervous system disorders
Dysgeusia	5/209 (2.4%)		14/208 (6.7%)
Neuropathy peripheral	0/209 (0%)		23/208 (11.1%)
Peripheral sensory neuropathy	1/209 (0.5%)		48/208 (23.1%)
Psychiatric disorders
Insomnia	11/209 (5.3%)		13/208 (6.3%)
Respiratory, thoracic and mediastinal disorders
Cough	32/209 (15.3%)		25/208 (12%)
Dyspnoea	12/209 (5.7%)		8/208 (3.8%)
Skin and subcutaneous tissue disorders
Alopecia	3/209 (1.4%)		100/208 (48.1%)
Pruritus	26/209 (12.4%)		15/208 (7.2%)
Rash	26/209 (12.4%)		40/208 (19.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.