Trial Outcomes & Findings for Patritumab With Cetuximab and a Platinum Agent for Squamous Cell Carcinoma (Cancer) of the Head and Neck (SCCHN ) (NCT NCT02633800)

Last Updated: 2019-01-07

Results Overview

PFS is defined as the time from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever comes first. Median PFS is from Kaplan-Meier analysis. Confidence interval (CI) for median was computed using Brookmeyer-Crowley method.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

87 participants

Primary outcome timeframe

from Day 0 to end of active study (study termination) - within 12 months

Results posted on

2019-01-07

Participant Flow

Of 125 screened, 87 patients from 8 countries were randomized into treatment groups

Participant milestones

Participant milestones
Measure	Patritumab All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	Placebo All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin)
Overall Study STARTED	44	43
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	44	43

Reasons for withdrawal

Reasons for withdrawal
Measure	Patritumab All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	Placebo All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin)
Overall Study Death	3	3
Overall Study Reason not provided	1	0
Overall Study Radiologic(al) progression	23	23
Overall Study Clinical progression	3	6
Overall Study Study terminated by sponsor	6	5
Overall Study Adverse event, non-fatal	7	2
Overall Study Withdrawal by Subject	0	3
Overall Study Patient Request	1	1

Baseline Characteristics

Patritumab With Cetuximab and a Platinum Agent for Squamous Cell Carcinoma (Cancer) of the Head and Neck (SCCHN )

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Patritumab n=44 Participants All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	Placebo n=43 Participants All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	Total n=87 Participants Total of all reporting groups
Age, Continuous	57.3 years STANDARD_DEVIATION 9.18 • n=5 Participants	61.0 years STANDARD_DEVIATION 9.19 • n=7 Participants	59.1 years STANDARD_DEVIATION 9.33 • n=5 Participants
Age, Customized 18-64 Years	32 Participants n=5 Participants	27 Participants n=7 Participants	59 Participants n=5 Participants
Age, Customized 65-84 Years	12 Participants n=5 Participants	16 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	36 Participants n=7 Participants	72 Participants n=5 Participants
Race/Ethnicity, Customized White	37 Participants n=5 Participants	37 Participants n=7 Participants	74 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other, Not Specified	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment Romania	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Belgium	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Hungary	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants
Region of Enrollment Poland	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United Kingdom	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment France	9 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment Germany	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0=Fully active	19 Participants n=5 Participants	22 Participants n=7 Participants	41 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1=Restricted in Physically Strenuous Activity	25 Participants n=5 Participants	20 Participants n=7 Participants	45 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2=Ambulatory and Capable of All Self-Care	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: from Day 0 to end of active study (study termination) - within 12 months

Population: Participants in the heregulin-high expression population

Outcome measures

Outcome measures
Measure	Patritumab n=26 Participants All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	Placebo n=25 Participants All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin)
Progression Free Survival (PFS) in the Heregulin (HRG)-High Expression Population	5.56 months Interval 4.08 to 11.18	5.56 months Interval 3.06 to 8.29

SECONDARY outcome

Timeframe: at approximately 25 months

Population: The trial terminated before sufficient data were collected for this analysis (at approximately 12 months which is prior to the time point for this analysis).

Overall survival (OS) is defined as the time from the date of randomization to death due to any cause

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: at approximately 22 months

Population: The trial terminated before sufficient data were collected for this analysis (at approximately 12 months which is prior to the time point for this analysis).

Best overall response rate (ORR) is defined as the percentage of participants with Complete Response (CR) or Partial Response (PR)

Outcome measures

Outcome data not reported

Adverse Events

Patritumab

Serious events: 19 serious events

Other events: 44 other events

Deaths: 24 deaths

Placebo

Serious events: 16 serious events

Other events: 42 other events

Deaths: 20 deaths

Serious adverse events

Other adverse events

Additional Information

Global Clinical Leader

Daiichi Sankyo, Inc.

Phone: 9089926400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Patritumab n=44 participants at risk All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	Placebo n=43 participants at risk All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	9.3% 4/43 • Number of events 4 • Adverse events were collected until trial termination at 12 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	4.5% 2/44 • Number of events 2 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Immune system disorders Anaphylactic shock	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Immune system disorders Hypersensitivity	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
General disorders Asthenia	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
General disorders General physical health deterioration	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 2 • Adverse events were collected until trial termination at 12 months.
General disorders Localised oedema	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
General disorders Non-cardiac chest pain	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
General disorders Malaise	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Injury, poisoning and procedural complications Fall	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Injury, poisoning and procedural complications Head Injury	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Investigations Ejection Fraction Decreased	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Investigations Neutrophil count decreased	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Investigations Weight decreased	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Cardiac disorders Acute Coronary Syndrome	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Cardiac disorders Arrhythmia	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Cardiac disorders Cardiac Disorder	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Cardiac disorders Cardiovascular insufficiency	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Cardiac disorders Myocardial ischaemia	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Cardiac disorders Sinus tachycardia	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Respiratory, thoracic and mediastinal disorders Acquired tracheo-oesophageal fistula	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Respiratory, thoracic and mediastinal disorders Lower respiratory tract congestion	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Respiratory, thoracic and mediastinal disorders Respiratory distress	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Blood and lymphatic system disorders Anaemia	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Blood and lymphatic system disorders Febrile neutropenia	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Nervous system disorders Dizziness	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Nervous system disorders Loss of consciousness	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Nervous system disorders Syncope	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Ear and labyrinth disorders Vertigo	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Gastrointestinal disorders Abdominal pain	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Gastrointestinal disorders Diarrhoea	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 2 • Adverse events were collected until trial termination at 12 months.
Gastrointestinal disorders Dysphagia	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Gastrointestinal disorders Melaena	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Gastrointestinal disorders Nausea	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Gastrointestinal disorders Oral pain	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Renal and urinary disorders Renal failure	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Renal and urinary disorders Renal Impairment	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Musculoskeletal and connective tissue disorders Osteonecrosis	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Metabolism and nutrition disorders Cachexia	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Metabolism and nutrition disorders Decreased Appetite	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Metabolism and nutrition disorders Dehydration	6.8% 3/44 • Number of events 4 • Adverse events were collected until trial termination at 12 months.	4.7% 2/43 • Number of events 2 • Adverse events were collected until trial termination at 12 months.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Metabolism and nutrition disorders Hypokalaemia	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Metabolism and nutrition disorders Hyponatraemia	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Infections and infestations Arthritis bacterial	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Infections and infestations Catheter site infection	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Infections and infestations Device related infection	4.5% 2/44 • Number of events 2 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Infections and infestations Empyema	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Infections and infestations Gastroenteritis	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Infections and infestations Lymphangitis	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Infections and infestations Pneumonia	9.1% 4/44 • Number of events 7 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Infections and infestations Sepsis	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	4.7% 2/43 • Number of events 2 • Adverse events were collected until trial termination at 12 months.

Measure	Patritumab n=44 participants at risk All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin)	Placebo n=43 participants at risk All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin)
Respiratory, thoracic and mediastinal disorders Cough	11.4% 5/44 • Number of events 7 • Adverse events were collected until trial termination at 12 months.	11.6% 5/43 • Number of events 5 • Adverse events were collected until trial termination at 12 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	15.9% 7/44 • Number of events 12 • Adverse events were collected until trial termination at 12 months.	11.6% 5/43 • Number of events 8 • Adverse events were collected until trial termination at 12 months.
Vascular disorders Hypertension	4.5% 2/44 • Number of events 2 • Adverse events were collected until trial termination at 12 months.	7.0% 3/43 • Number of events 4 • Adverse events were collected until trial termination at 12 months.
Vascular disorders Hypotension	6.8% 3/44 • Number of events 3 • Adverse events were collected until trial termination at 12 months.	9.3% 4/43 • Number of events 5 • Adverse events were collected until trial termination at 12 months.
General disorders Asthenia	22.7% 10/44 • Number of events 14 • Adverse events were collected until trial termination at 12 months.	25.6% 11/43 • Number of events 17 • Adverse events were collected until trial termination at 12 months.
General disorders Chills	9.1% 4/44 • Number of events 5 • Adverse events were collected until trial termination at 12 months.	4.7% 2/43 • Number of events 2 • Adverse events were collected until trial termination at 12 months.
General disorders Fatigue	25.0% 11/44 • Number of events 14 • Adverse events were collected until trial termination at 12 months.	16.3% 7/43 • Number of events 9 • Adverse events were collected until trial termination at 12 months.
General disorders Mucosal inflammation	18.2% 8/44 • Number of events 13 • Adverse events were collected until trial termination at 12 months.	4.7% 2/43 • Number of events 2 • Adverse events were collected until trial termination at 12 months.
General disorders Oedema peripheral	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	7.0% 3/43 • Number of events 3 • Adverse events were collected until trial termination at 12 months.
General disorders Pyrexia	9.1% 4/44 • Number of events 7 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Psychiatric disorders Anxiety	4.5% 2/44 • Number of events 2 • Adverse events were collected until trial termination at 12 months.	7.0% 3/43 • Number of events 3 • Adverse events were collected until trial termination at 12 months.
Psychiatric disorders Depression	4.5% 2/44 • Number of events 2 • Adverse events were collected until trial termination at 12 months.	7.0% 3/43 • Number of events 3 • Adverse events were collected until trial termination at 12 months.
Psychiatric disorders Insomnia	9.1% 4/44 • Number of events 4 • Adverse events were collected until trial termination at 12 months.	9.3% 4/43 • Number of events 6 • Adverse events were collected until trial termination at 12 months.
Investigations Alanine aminotransferase increased	6.8% 3/44 • Number of events 6 • Adverse events were collected until trial termination at 12 months.	4.7% 2/43 • Number of events 2 • Adverse events were collected until trial termination at 12 months.
Investigations Aspartate aminotransferase increased	6.8% 3/44 • Number of events 5 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Investigations Blood alkaline phosphatase increased	6.8% 3/44 • Number of events 6 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Investigations Neutrophil count decreased	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	7.0% 3/43 • Number of events 4 • Adverse events were collected until trial termination at 12 months.
Investigations Weight Decreased	25.0% 11/44 • Number of events 16 • Adverse events were collected until trial termination at 12 months.	23.3% 10/43 • Number of events 12 • Adverse events were collected until trial termination at 12 months.
Investigations Weight increased	2.3% 1/44 • Number of events 1 • Adverse events were collected until trial termination at 12 months.	7.0% 3/43 • Number of events 5 • Adverse events were collected until trial termination at 12 months.
Cardiac disorders Tachycardia	6.8% 3/44 • Number of events 5 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Blood and lymphatic system disorders Anaemia	40.9% 18/44 • Number of events 34 • Adverse events were collected until trial termination at 12 months.	30.2% 13/43 • Number of events 22 • Adverse events were collected until trial termination at 12 months.
Blood and lymphatic system disorders Leukocytosis	11.4% 5/44 • Number of events 5 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Blood and lymphatic system disorders Neutropenia	29.5% 13/44 • Number of events 23 • Adverse events were collected until trial termination at 12 months.	25.6% 11/43 • Number of events 22 • Adverse events were collected until trial termination at 12 months.
Blood and lymphatic system disorders Thrombocytopenia	22.7% 10/44 • Number of events 20 • Adverse events were collected until trial termination at 12 months.	32.6% 14/43 • Number of events 39 • Adverse events were collected until trial termination at 12 months.
Respiratory, thoracic and mediastinal disorders Haemoptysis	9.1% 4/44 • Number of events 5 • Adverse events were collected until trial termination at 12 months.	7.0% 3/43 • Number of events 3 • Adverse events were collected until trial termination at 12 months.
Nervous system disorders Dizziness	9.1% 4/44 • Number of events 4 • Adverse events were collected until trial termination at 12 months.	4.7% 2/43 • Number of events 2 • Adverse events were collected until trial termination at 12 months.
Nervous system disorders Dysgeusia	9.1% 4/44 • Number of events 4 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Nervous system disorders Headache	6.8% 3/44 • Number of events 4 • Adverse events were collected until trial termination at 12 months.	11.6% 5/43 • Number of events 6 • Adverse events were collected until trial termination at 12 months.
Nervous system disorders Paraesthesia	6.8% 3/44 • Number of events 3 • Adverse events were collected until trial termination at 12 months.	0.00% 0/43 • Adverse events were collected until trial termination at 12 months.
Ear and labyrinth disorders Tinnitus	9.1% 4/44 • Number of events 4 • Adverse events were collected until trial termination at 12 months.	4.7% 2/43 • Number of events 2 • Adverse events were collected until trial termination at 12 months.
Gastrointestinal disorders Constipation	15.9% 7/44 • Number of events 7 • Adverse events were collected until trial termination at 12 months.	11.6% 5/43 • Number of events 7 • Adverse events were collected until trial termination at 12 months.
Gastrointestinal disorders Diarrhoea	27.3% 12/44 • Number of events 18 • Adverse events were collected until trial termination at 12 months.	11.6% 5/43 • Number of events 6 • Adverse events were collected until trial termination at 12 months.
Gastrointestinal disorders Dysphagia	18.2% 8/44 • Number of events 10 • Adverse events were collected until trial termination at 12 months.	9.3% 4/43 • Number of events 4 • Adverse events were collected until trial termination at 12 months.
Gastrointestinal disorders Gastrooesophageal Reflux Disease	9.1% 4/44 • Number of events 4 • Adverse events were collected until trial termination at 12 months.	4.7% 2/43 • Number of events 2 • Adverse events were collected until trial termination at 12 months.
Gastrointestinal disorders Nausea	36.4% 16/44 • Number of events 23 • Adverse events were collected until trial termination at 12 months.	32.6% 14/43 • Number of events 22 • Adverse events were collected until trial termination at 12 months.
Gastrointestinal disorders Oral Pain	6.8% 3/44 • Number of events 3 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Gastrointestinal disorders Stomatitis	11.4% 5/44 • Number of events 9 • Adverse events were collected until trial termination at 12 months.	7.0% 3/43 • Number of events 3 • Adverse events were collected until trial termination at 12 months.
Gastrointestinal disorders Vomiting	20.5% 9/44 • Number of events 11 • Adverse events were collected until trial termination at 12 months.	16.3% 7/43 • Number of events 14 • Adverse events were collected until trial termination at 12 months.
Skin and subcutaneous tissue disorders Dermatitis acneiform	34.1% 15/44 • Number of events 20 • Adverse events were collected until trial termination at 12 months.	18.6% 8/43 • Number of events 17 • Adverse events were collected until trial termination at 12 months.
Skin and subcutaneous tissue disorders Dry skin	13.6% 6/44 • Number of events 7 • Adverse events were collected until trial termination at 12 months.	16.3% 7/43 • Number of events 8 • Adverse events were collected until trial termination at 12 months.
Skin and subcutaneous tissue disorders Pruritus	6.8% 3/44 • Number of events 3 • Adverse events were collected until trial termination at 12 months.	7.0% 3/43 • Number of events 3 • Adverse events were collected until trial termination at 12 months.
Skin and subcutaneous tissue disorders Rash	45.5% 20/44 • Number of events 42 • Adverse events were collected until trial termination at 12 months.	48.8% 21/43 • Number of events 28 • Adverse events were collected until trial termination at 12 months.
Skin and subcutaneous tissue disorders Rash Maculo-Papular	6.8% 3/44 • Number of events 5 • Adverse events were collected until trial termination at 12 months.	4.7% 2/43 • Number of events 2 • Adverse events were collected until trial termination at 12 months.
Skin and subcutaneous tissue disorders Skin fissures	15.9% 7/44 • Number of events 8 • Adverse events were collected until trial termination at 12 months.	14.0% 6/43 • Number of events 13 • Adverse events were collected until trial termination at 12 months.
Skin and subcutaneous tissue disorders Skin toxicity	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	7.0% 3/43 • Number of events 3 • Adverse events were collected until trial termination at 12 months.
Musculoskeletal and connective tissue disorders Back pain	9.1% 4/44 • Number of events 4 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Musculoskeletal and connective tissue disorders Neck pain	6.8% 3/44 • Number of events 6 • Adverse events were collected until trial termination at 12 months.	9.3% 4/43 • Number of events 10 • Adverse events were collected until trial termination at 12 months.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/44 • Adverse events were collected until trial termination at 12 months.	7.0% 3/43 • Number of events 3 • Adverse events were collected until trial termination at 12 months.
Metabolism and nutrition disorders Decreased appetite	25.0% 11/44 • Number of events 14 • Adverse events were collected until trial termination at 12 months.	25.6% 11/43 • Number of events 17 • Adverse events were collected until trial termination at 12 months.
Metabolism and nutrition disorders Hypercalcaemia	6.8% 3/44 • Number of events 3 • Adverse events were collected until trial termination at 12 months.	7.0% 3/43 • Number of events 3 • Adverse events were collected until trial termination at 12 months.
Metabolism and nutrition disorders Hypokalaemia	25.0% 11/44 • Number of events 15 • Adverse events were collected until trial termination at 12 months.	4.7% 2/43 • Number of events 5 • Adverse events were collected until trial termination at 12 months.
Metabolism and nutrition disorders Hypomagnesaemia	36.4% 16/44 • Number of events 29 • Adverse events were collected until trial termination at 12 months.	34.9% 15/43 • Number of events 35 • Adverse events were collected until trial termination at 12 months.
Metabolism and nutrition disorders Hyponatraemia	6.8% 3/44 • Number of events 4 • Adverse events were collected until trial termination at 12 months.	2.3% 1/43 • Number of events 1 • Adverse events were collected until trial termination at 12 months.
Metabolism and nutrition disorders Hypophosphataemia	4.5% 2/44 • Number of events 6 • Adverse events were collected until trial termination at 12 months.	11.6% 5/43 • Number of events 12 • Adverse events were collected until trial termination at 12 months.
Infections and infestations Conjunctivitis	13.6% 6/44 • Number of events 6 • Adverse events were collected until trial termination at 12 months.	9.3% 4/43 • Number of events 5 • Adverse events were collected until trial termination at 12 months.
Infections and infestations Folliculitis	4.5% 2/44 • Number of events 3 • Adverse events were collected until trial termination at 12 months.	11.6% 5/43 • Number of events 6 • Adverse events were collected until trial termination at 12 months.
Infections and infestations Paronychia	34.1% 15/44 • Number of events 25 • Adverse events were collected until trial termination at 12 months.	9.3% 4/43 • Number of events 4 • Adverse events were collected until trial termination at 12 months.