Trial Outcomes & Findings for Radiotherapy With Pembrolizumab in Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) (NCT NCT03386357)

Last Updated: 2026-03-27

Results Overview

Response evaluation will be performed according to iRECIST and RECIST. These iRECIST criteria are the RECIST 1.1 criteria adapted for immunotherapy. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the small

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

115 participants

Primary outcome timeframe

Endpoint is the best response during pembrolizumab treatment (restaging every 9 weeks up to 12 months)

Results posted on

2026-03-27

Participant Flow

Participant milestones

Participant milestones
Measure	A (Pembrolizumab+RT) Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. A (pembrolizumab+RT): Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. Only metastases that perspectively require radiotherapy will be treated. The irradiated tumor volume must be at least 10cm³. Radiotherapy of brain metastases is not allowed.	B (Pembrolizumab) Pembrolizumab (200mg absolute, q3w) without radiotherapy B (pembrolizumab): Pembrolizumab (200mg absolute, q3w)
Overall Study STARTED	57	58
Overall Study COMPLETED	57	58
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	A (Pembrolizumab+RT) n=57 Participants Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. A (pembrolizumab+RT): Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. Only metastases that perspectively require radiotherapy will be treated. The irradiated tumor volume must be at least 10cm³. Radiotherapy of brain metastases is not allowed.	B (Pembrolizumab) n=58 Participants Pembrolizumab (200mg absolute, q3w) without radiotherapy B (pembrolizumab): Pembrolizumab (200mg absolute, q3w)	Total n=115 Participants Total of all reporting groups
Sex: Female, Male Male	48 Participants n=57 Participants	54 Participants n=58 Participants	102 Participants n=115 Participants
Age, Categorical <=18 years	0 Participants n=57 Participants	0 Participants n=58 Participants	0 Participants n=115 Participants
Age, Categorical Between 18 and 65 years	21 Participants n=57 Participants	31 Participants n=58 Participants	52 Participants n=115 Participants
Age, Categorical >=65 years	36 Participants n=57 Participants	27 Participants n=58 Participants	63 Participants n=115 Participants
Age, Continuous	66.7 years STANDARD_DEVIATION 9.9 • n=57 Participants	62.8 years STANDARD_DEVIATION 9.2 • n=58 Participants	64.7 years STANDARD_DEVIATION 9.7 • n=115 Participants
Sex: Female, Male Female	9 Participants n=57 Participants	4 Participants n=58 Participants	13 Participants n=115 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Germany	57 participants n=57 Participants	58 participants n=58 Participants	115 participants n=115 Participants

PRIMARY outcome

Timeframe: Endpoint is the best response during pembrolizumab treatment (restaging every 9 weeks up to 12 months)

Outcome measures

Outcome measures
Measure	A (Pembrolizumab+RT) n=57 Participants Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. A (pembrolizumab+RT): Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. Only metastases that perspectively require radiotherapy will be treated. The irradiated tumor volume must be at least 10cm³. Radiotherapy of brain metastases is not allowed.	B (Pembrolizumab) n=58 Participants Pembrolizumab (200mg absolute, q3w) without radiotherapy B (pembrolizumab): Pembrolizumab (200mg absolute, q3w)
Best Response According to iRECIST Criteria immune partial response (iPR)	14 Participants	10 Participants
Best Response According to iRECIST Criteria immune stable disease (iSD)	9 Participants	10 Participants
Best Response According to iRECIST Criteria immune progressive disease (iPD), confirmed	5 Participants	10 Participants
Best Response According to iRECIST Criteria iPD, unconfirmed	10 Participants	10 Participants
Best Response According to iRECIST Criteria missing iRECIST result	0 Participants	3 Participants
Best Response According to iRECIST Criteria no restaging	2 Participants	8 Participants
Best Response According to iRECIST Criteria not qualified for per-protocol analysis	11 Participants	4 Participants
Best Response According to iRECIST Criteria immune complete response (iCR)	6 Participants	3 Participants

SECONDARY outcome

Timeframe: restaging every 9 weeks up to 12 months

RECIST 1.1 criteria will be used to evaluate response rate

Outcome measures

Outcome measures
Measure	A (Pembrolizumab+RT) n=57 Participants Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. A (pembrolizumab+RT): Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. Only metastases that perspectively require radiotherapy will be treated. The irradiated tumor volume must be at least 10cm³. Radiotherapy of brain metastases is not allowed.	B (Pembrolizumab) n=58 Participants Pembrolizumab (200mg absolute, q3w) without radiotherapy B (pembrolizumab): Pembrolizumab (200mg absolute, q3w)
Response Rate According to RECIST PD	19 Participants	21 Participants
Response Rate According to RECIST missing RECIST result	0 Participants	1 Participants
Response Rate According to RECIST no restaging	10 Participants	11 Participants
Response Rate According to RECIST CR	6 Participants	3 Participants
Response Rate According to RECIST PR	13 Participants	11 Participants
Response Rate According to RECIST SD	9 Participants	11 Participants

SECONDARY outcome

Timeframe: restaging every 9 weeks up to 12 months

The duration of the response will be evaluated in responding patients.

Outcome measures

Outcome measures
Measure	A (Pembrolizumab+RT) n=20 Participants Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. A (pembrolizumab+RT): Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. Only metastases that perspectively require radiotherapy will be treated. The irradiated tumor volume must be at least 10cm³. Radiotherapy of brain metastases is not allowed.	B (Pembrolizumab) n=13 Participants Pembrolizumab (200mg absolute, q3w) without radiotherapy B (pembrolizumab): Pembrolizumab (200mg absolute, q3w)
Assessment of the Duration of Response	13.65 months Standard Error 3.03	8.91 months Standard Error 1.80

SECONDARY outcome

Timeframe: restaging every 9 weeks up to 12 months

progression free survival in ITT population Response evaluation will be performed according to iRECIST and RECIST. These iRECIST criteria are the RECIST 1.1 criteria adapted for immunotherapy. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Outcome measures

Outcome measures
Measure	A (Pembrolizumab+RT) n=57 Participants Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. A (pembrolizumab+RT): Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. Only metastases that perspectively require radiotherapy will be treated. The irradiated tumor volume must be at least 10cm³. Radiotherapy of brain metastases is not allowed.	B (Pembrolizumab) n=58 Participants Pembrolizumab (200mg absolute, q3w) without radiotherapy B (pembrolizumab): Pembrolizumab (200mg absolute, q3w)
Assessment of the Progression Free Survival	4.2 months Interval 2.1 to 10.4	4.0 months Interval 2.1 to 10.4

SECONDARY outcome

Timeframe: during trial treatment an follow-up, i.e. total of 24 months

Overall survival (in months) in ITT population

Outcome measures

Outcome measures
Measure	A (Pembrolizumab+RT) n=57 Participants Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. A (pembrolizumab+RT): Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. Only metastases that perspectively require radiotherapy will be treated. The irradiated tumor volume must be at least 10cm³. Radiotherapy of brain metastases is not allowed.	B (Pembrolizumab) n=58 Participants Pembrolizumab (200mg absolute, q3w) without radiotherapy B (pembrolizumab): Pembrolizumab (200mg absolute, q3w)
Assessment of the Overall Survival	11.4 months Interval 8.2 to 18.4	11.3 months Interval 8.6 to 19.6

SECONDARY outcome

Timeframe: at every pembrolizumab administration (q3w) (up tp 12 months)

Toxicity will be evaluated according to CTCAE 4.0 to assess toxicity of the combination of pembrolizumab and radiotherapy

Outcome measures

Outcome measures
Measure	A (Pembrolizumab+RT) n=57 Participants Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. A (pembrolizumab+RT): Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. Only metastases that perspectively require radiotherapy will be treated. The irradiated tumor volume must be at least 10cm³. Radiotherapy of brain metastases is not allowed.	B (Pembrolizumab) n=58 Participants Pembrolizumab (200mg absolute, q3w) without radiotherapy B (pembrolizumab): Pembrolizumab (200mg absolute, q3w)
Assessment of Toxicity of the Combination of Pembrolizumab and Radiotherapy total no. of adverse events	562 events	639 events
Assessment of Toxicity of the Combination of Pembrolizumab and Radiotherapy total no. of severe adverse events	47 events	52 events
Assessment of Toxicity of the Combination of Pembrolizumab and Radiotherapy no. of adverse events grade 3 to 5	68 events	78 events

Adverse Events

A (Pembrolizumab+RT)

Serious events: 26 serious events

Other events: 54 other events

Deaths: 39 deaths

B (Pembrolizumab)

Serious events: 32 serious events

Other events: 56 other events

Deaths: 40 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Philipp Schubert

Universitätsklinkum Erlangen, Strahlenklinik

Phone: +49 9131

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	A (Pembrolizumab+RT) n=57 participants at risk Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. A (pembrolizumab+RT): Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. Only metastases that perspectively require radiotherapy will be treated. The irradiated tumor volume must be at least 10cm³. Radiotherapy of brain metastases is not allowed.	B (Pembrolizumab) n=58 participants at risk Pembrolizumab (200mg absolute, q3w) without radiotherapy B (pembrolizumab): Pembrolizumab (200mg absolute, q3w)
Cardiac disorders Cardiac failure	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	0.00% 0/58 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Gastrointestinal disorders Dysphagia	7.0% 4/57 • Number of events 4 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Gastrointestinal disorders Gastritis	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Gastrointestinal disorders Nausea	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Gastrointestinal disorders Oral Pain	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	0.00% 0/58 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Gastrointestinal disorders Pneumatosis intestinalis	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	0.00% 0/58 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	0.00% 0/58 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Gastrointestinal disorders Vomiting	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	3.4% 2/58 • Number of events 2 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
General disorders Asthenia	3.5% 2/57 • Number of events 2 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	0.00% 0/58 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
General disorders Complication associated with device	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
General disorders Death	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
General disorders General physical health deterioration	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
General disorders Pain	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	0.00% 0/58 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
General disorders Pyrexia	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	3.4% 2/58 • Number of events 2 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Hepatobiliary disorders Hepatotoxicity	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	0.00% 0/58 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Immune system disorders Hypersensitivity	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	0.00% 0/58 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Infections and infestations Appendicitis	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Infections and infestations COVID-19	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	3.4% 2/58 • Number of events 2 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Infections and infestations Infection	7.0% 4/57 • Number of events 5 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	10.3% 6/58 • Number of events 6 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Infections and infestations Nosocomial infection	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	0.00% 0/58 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Infections and infestations Pneumonia	7.0% 4/57 • Number of events 5 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	5.2% 3/58 • Number of events 3 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Infections and infestations Sepsis	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	0.00% 0/58 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Infections and infestations Tracheostomy infection	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Infections and infestations Wound infection	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Injury, poisoning and procedural complications Fall	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	0.00% 0/58 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Injury, poisoning and procedural complications Femoral neck fracture	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	0.00% 0/58 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Investigations C-reactive protein increased	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Investigations Transaminases increased	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	0.00% 0/58 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Metabolism and nutrition disorders Dehydration	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Metabolism and nutrition disorders Hypercalcemia	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	3.4% 2/58 • Number of events 5 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Metabolism and nutrition disorders Hyponatremia	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 2 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Musculoskeletal and connective tissue disorders Neck mass	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	0.00% 0/58 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Musculoskeletal and connective tissue disorders Spinal instability	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to spine	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor hemorrhage	3.5% 2/57 • Number of events 2 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	3.4% 2/58 • Number of events 2 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Nervous system disorders Syncope	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	3.4% 2/58 • Number of events 2 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Nervous system disorders Seizure	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	0.00% 0/58 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).

Other adverse events
Measure	A (Pembrolizumab+RT) n=57 participants at risk Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. A (pembrolizumab+RT): Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. Only metastases that perspectively require radiotherapy will be treated. The irradiated tumor volume must be at least 10cm³. Radiotherapy of brain metastases is not allowed.	B (Pembrolizumab) n=58 participants at risk Pembrolizumab (200mg absolute, q3w) without radiotherapy B (pembrolizumab): Pembrolizumab (200mg absolute, q3w)
Blood and lymphatic system disorders Anemia	14.0% 8/57 • Number of events 8 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	19.0% 11/58 • Number of events 11 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Blood and lymphatic system disorders Leukocytosis	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	5.2% 3/58 • Number of events 3 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Ear and labyrinth disorders Hearing impaired	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	5.2% 3/58 • Number of events 3 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Ear and labyrinth disorders Vertigo	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	5.2% 3/58 • Number of events 3 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Endocrine disorders Hyperthyroidism	5.3% 3/57 • Number of events 3 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	3.4% 2/58 • Number of events 2 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Endocrine disorders Hypothyroidism	12.3% 7/57 • Number of events 7 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	12.1% 7/58 • Number of events 7 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Gastrointestinal disorders Constipation	22.8% 13/57 • Number of events 13 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	20.7% 12/58 • Number of events 12 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Gastrointestinal disorders Diarrhea	12.3% 7/57 • Number of events 7 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	20.7% 12/58 • Number of events 12 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Gastrointestinal disorders Dry mouth	21.1% 12/57 • Number of events 12 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	17.2% 10/58 • Number of events 10 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Gastrointestinal disorders Dysphagia	8.8% 5/57 • Number of events 5 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	20.7% 12/58 • Number of events 12 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Gastrointestinal disorders Mucositis oral	38.6% 22/57 • Number of events 22 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	25.9% 15/58 • Number of events 15 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Gastrointestinal disorders Nausea	24.6% 14/57 • Number of events 14 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	29.3% 17/58 • Number of events 17 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Gastrointestinal disorders Vomiting	12.3% 7/57 • Number of events 7 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
General disorders Edema face	3.5% 2/57 • Number of events 2 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	10.3% 6/58 • Number of events 6 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
General disorders Edema limbs	3.5% 2/57 • Number of events 2 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	8.6% 5/58 • Number of events 5 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
General disorders Fatigue	40.4% 23/57 • Number of events 23 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	48.3% 28/58 • Number of events 28 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
General disorders Pain	38.6% 22/57 • Number of events 22 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	36.2% 21/58 • Number of events 21 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Infections and infestations Abdominal infection	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	10.3% 6/58 • Number of events 6 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Infections and infestations Infection and infestations - other	28.1% 16/57 • Number of events 16 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	17.2% 10/58 • Number of events 10 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Infections and infestations Lung infection	7.0% 4/57 • Number of events 4 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	6.9% 4/58 • Number of events 4 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Infections and infestations Mucosal infection	3.5% 2/57 • Number of events 2 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	13.8% 8/58 • Number of events 8 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Infections and infestations Stoma site infection	7.0% 4/57 • Number of events 4 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	3.4% 2/58 • Number of events 2 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Nervous system disorders Dizziness	15.8% 9/57 • Number of events 9 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	20.7% 12/58 • Number of events 12 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Injury, poisoning and procedural complications Dermation radiation	17.5% 10/57 • Number of events 10 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Injury, poisoning and procedural complications Injury, poisoning and procedural - other	5.3% 3/57 • Number of events 3 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	3.4% 2/58 • Number of events 2 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Investigations Alanine aminotransferase increased	7.0% 4/57 • Number of events 4 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	15.5% 9/58 • Number of events 9 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Investigations Alkaline phosphatase increased	1.8% 1/57 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	8.6% 5/58 • Number of events 5 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Investigations Aspartate aminotransferase increased	5.3% 3/57 • Number of events 3 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	15.5% 9/58 • Number of events 9 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Investigations Blood corticotrophin decreased	7.0% 4/57 • Number of events 4 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	1.7% 1/58 • Number of events 1 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Investigations GGT increased	5.3% 3/57 • Number of events 3 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	13.8% 8/58 • Number of events 8 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Investigations Investigations - Other	29.8% 17/57 • Number of events 17 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	34.5% 20/58 • Number of events 20 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Investigations Lymphocyte count decreased	12.3% 7/57 • Number of events 7 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	19.0% 11/58 • Number of events 11 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Investigations Weight loss	8.8% 5/57 • Number of events 5 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	10.3% 6/58 • Number of events 6 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Metabolism and nutrition disorders Hypercalcemia	8.8% 5/57 • Number of events 5 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	10.3% 6/58 • Number of events 6 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Metabolism and nutrition disorders Hyperkalemia	3.5% 2/57 • Number of events 2 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	10.3% 6/58 • Number of events 6 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Metabolism and nutrition disorders Hypokalemia	10.5% 6/57 • Number of events 6 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	6.9% 4/58 • Number of events 4 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Metabolism and nutrition disorders Hypomagnesemia	7.0% 4/57 • Number of events 4 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	12.1% 7/58 • Number of events 7 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Metabolism and nutrition disorders Hyponatremia	21.1% 12/57 • Number of events 12 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	15.5% 9/58 • Number of events 9 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other	7.0% 4/57 • Number of events 4 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	3.4% 2/58 • Number of events 2 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).
Nervous system disorders Peripheral motor neuropathy	0.00% 0/57 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).	5.2% 3/58 • Number of events 3 • From the time of treatment allocation/ randomization through 30 days following cessation of treatment, all AEs must be reported (i.e. up to 18 months) Adverse events were recorded and graded according to NCI-CTCAE V.4, with individual items sorted to 22 system organ classes (SOC).