Trial Outcomes & Findings for Study of Mutation-Targeted Therapy With Sunitinib or Everolimus in People With Advanced Low- or Intermediate-Grade Neuroendocrine Tumors of the Gastrointestinal Tract and Pancreas With or Without Cytoreductive Surgery (NCT NCT02315625)

Last Updated: 2020-09-09

Results Overview

Median amount of time subject survives without disease progression after treatment. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is at least a 20% increase in the sum of the 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. The appearance of one or more new lesions is also considered progressions.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

Up to approximately 2 years

Results posted on

2020-09-09

Participant Flow

Study closed due to poor accrual.

Participant milestones

Participant milestones
Measure	Sunitinib Followed by Everolimus In Period 1 participants received Sunitinib 37.5 mg once daily until progression or unacceptable treatment-related toxicity. In Period 2 participants received Everolimus 10 mg daily until progression or unacceptable treatment-related toxicity.	Everolimus Followed by Sunitinib In Period 1 participants received Everolimus 10 mg daily until progression or unacceptable treatment-related toxicity. In Period 2 participants received Sunitinib 37.5 mg once daily until progression or unacceptable treatment-related toxicity.
First Intervention STARTED	14	2
First Intervention COMPLETED	13	2
First Intervention NOT COMPLETED	1	0
Second Intervention STARTED	13	2
Second Intervention COMPLETED	9	1
Second Intervention NOT COMPLETED	4	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Sunitinib Followed by Everolimus In Period 1 participants received Sunitinib 37.5 mg once daily until progression or unacceptable treatment-related toxicity. In Period 2 participants received Everolimus 10 mg daily until progression or unacceptable treatment-related toxicity.	Everolimus Followed by Sunitinib In Period 1 participants received Everolimus 10 mg daily until progression or unacceptable treatment-related toxicity. In Period 2 participants received Sunitinib 37.5 mg once daily until progression or unacceptable treatment-related toxicity.
First Intervention Disease Progression	1	0
Second Intervention Physician Decision	2	1
Second Intervention Study closure	1	0
Second Intervention Disease Progression	1	0

Baseline Characteristics

Study of Mutation-Targeted Therapy With Sunitinib or Everolimus in People With Advanced Low- or Intermediate-Grade Neuroendocrine Tumors of the Gastrointestinal Tract and Pancreas With or Without Cytoreductive Surgery

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Up to approximately 2 years

Population: The data in this outcome measure is reported per sequence as pre-specified in the protocol.

Outcome measures

Outcome measures
Measure	Sunitinib First, Everolimus Second n=14 Participants Participants who received Sunitinib first, followed by Everolimus.	Everolimus First, Sunitinib Second n=2 Participants Participants who received Everolimus first, followed by Sunitinib.
Median Amount of Time Subject Survives Without Disease Progression After Treatment	7 months Interval 3.0 to 15.0	18 months Interval 0.0 to 18.0

SECONDARY outcome

Timeframe: Every 3 months until disease progression, up to 12 months

Population: The data in this outcome measure is reported per sequence as pre-specified in the protocol.

Overall response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) is defined as Complete Response (CR), Partial Response (PR), and Stable Disease (SD). Complete Response is 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 is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD) (e.g. appearance of one or more new lesions), taking as reference the smallest sum of diameters while on study.

Outcome measures

Outcome measures
Measure	Sunitinib First, Everolimus Second n=14 Participants Participants who received Sunitinib first, followed by Everolimus.	Everolimus First, Sunitinib Second n=2 Participants Participants who received Everolimus first, followed by Sunitinib.
Number of Participants With an Overall Response	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to approximately 4 years

Population: The data in this outcome measure is reported per sequence as pre-specified in the protocol.

Overall survival is defined as the time from treatment start date until date of death or date last known alive following therapy.

Outcome measures

Outcome measures
Measure	Sunitinib First, Everolimus Second n=14 Participants Participants who received Sunitinib first, followed by Everolimus.	Everolimus First, Sunitinib Second n=2 Participants Participants who received Everolimus first, followed by Sunitinib.
Overall Survival	25.5 Months Interval 6.0 to 39.0	10.7 Months Interval 0.427397 to 21.0

SECONDARY outcome

Timeframe: Death, an average of 12 months follow up

Population: The data in this outcome measure is reported per sequence as pre-specified in the protocol.

MST is the amount of time a subject survives after therapy.

Outcome measures

Outcome measures
Measure	Sunitinib First, Everolimus Second n=14 Participants Participants who received Sunitinib first, followed by Everolimus.	Everolimus First, Sunitinib Second n=2 Participants Participants who received Everolimus first, followed by Sunitinib.
Median Survival Time (MST)	9.5 Months Interval 0.4927 to 33.0	5.5 Months Interval 0.0 to 11.0

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study approximately 49 months and 9 days.

Population: One participant did not receive Sunitinib and 5 did not receive Everolimus.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Sunitinib First, Everolimus Second n=15 Participants Participants who received Sunitinib first, followed by Everolimus.	Everolimus First, Sunitinib Second n=11 Participants Participants who received Everolimus first, followed by Sunitinib.
Number of Participants With Serious and Non-Serious Adverse Events	15 Participants	11 Participants

Adverse Events

Sunitinib

Serious events: 3 serious events

Other events: 14 other events

Deaths: 1 deaths

Everolimus

Serious events: 2 serious events

Other events: 7 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Naris Nilubol

National Cancer Institute

Phone: 240-760-6154

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Sunitinib Followed by Everolimus n=14 Participants In Period 1 participants received Sunitinib 37.5 mg once daily until progression or unacceptable treatment-related toxicity. In Period 2 participants received Everolimus 10 mg daily until progression or unacceptable treatment-related toxicity.	Everolimus Followed by Sunitinib n=2 Participants In Period 1 participants received Everolimus 10 mg daily until progression or unacceptable treatment-related toxicity. In Period 2 participants received Sunitinib 37.5 mg once daily until progression or unacceptable treatment-related toxicity.	Total n=16 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants	0 Participants n=7 Participants	12 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Age, Continuous	52.94 years STANDARD_DEVIATION 8.49 • n=5 Participants	53.41 years STANDARD_DEVIATION 9.73 • n=7 Participants	53.17 years STANDARD_DEVIATION 9.11 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	2 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants	2 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	2 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants	2 participants n=7 Participants	16 participants n=5 Participants

Measure	Sunitinib n=15 participants at risk Participants who received Sunitinib in period 1 or 2.	Everolimus n=11 participants at risk Participants who received Everolimus in period 1 or 2.
Renal and urinary disorders Acute kidney injury	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Blood and lymphatic system disorders Anemia	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 3 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/15 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
General disorders Edema limbs	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Eye disorders Eye disorders - Other, amaurosis fugax	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Gastrointestinal disorders Gastric hemorrhage	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/15 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Metabolism and nutrition disorders Hypertriglyceridemia	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Metabolism and nutrition disorders Hypokalemia	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Respiratory, thoracic and mediastinal disorders Hypoxia	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, multiple myeloma	0.00% 0/15 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Infections and infestations Sepsis	0.00% 0/15 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Nervous system disorders Stroke	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Vascular disorders Thromboembolic event	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.

Measure	Sunitinib n=15 participants at risk Participants who received Sunitinib in period 1 or 2.	Everolimus n=11 participants at risk Participants who received Everolimus in period 1 or 2.
Gastrointestinal disorders Abdominal pain	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 6 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Psychiatric disorders Agitation	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Investigations Alanine aminotransferase increased	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Blood and lymphatic system disorders Anemia	20.0% 3/15 • Number of events 5 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	27.3% 3/11 • Number of events 5 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Metabolism and nutrition disorders Anorexia	0.00% 0/15 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Investigations Aspartate aminotransferase increased	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 2 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Cardiac disorders Atrial fibrillation	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Gastrointestinal disorders Bloating	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Nervous system disorders Cognitive disturbance	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Infections and infestations Conjunctivitis infective	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Investigations Creatinine increased	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Metabolism and nutrition disorders Dehydration	0.00% 0/15 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Gastrointestinal disorders Diarrhea	13.3% 2/15 • Number of events 6 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	18.2% 2/11 • Number of events 2 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Nervous system disorders Dizziness	6.7% 1/15 • Number of events 2 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Nervous system disorders Dysgeusia	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
General disorders Edema limbs	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
General disorders Fatigue	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Gastrointestinal disorders Gastrointestinal disorders - Other, GI bleed, oral lesion	0.00% 0/15 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	18.2% 2/11 • Number of events 2 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Psychiatric disorders Hallucinations	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/15 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Respiratory, thoracic and mediastinal disorders Hyperhidrosis	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Nervous system disorders Hypersomnia	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Vascular disorders Hypertension	26.7% 4/15 • Number of events 9 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Metabolism and nutrition disorders Hypertriglyceridemia	6.7% 1/15 • Number of events 2 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/15 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Metabolism and nutrition disorders Hypokalemia	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Metabolism and nutrition disorders Hypophosphatemia	20.0% 3/15 • Number of events 3 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Endocrine disorders Hypothyroidism	0.00% 0/15 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Investigations Lymphocyte count decreased	0.00% 0/15 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	18.2% 2/11 • Number of events 3 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Investigations Neutrophil count decreased	26.7% 4/15 • Number of events 10 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 2 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	20.0% 3/15 • Number of events 3 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Skin and subcutaneous tissue disorders Pruritus	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/15 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Gastrointestinal disorders Rectal hemorrhage	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Skin and subcutaneous tissue disorders Skin hypopigmentation	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	0.00% 0/11 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/15 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 4 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Ear and labyrinth disorders Vertigo	0.00% 0/15 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 2 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.
Investigations White blood cell decreased	6.7% 1/15 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.	9.1% 1/11 • Number of events 1 • Date treatment consent signed to date off study on up to 30 days after treatment discontinuation, approximately 49 months and 9 days.