Trial Outcomes & Findings for Guadecitabine and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer (NCT NCT02901899)

NCT ID: NCT02901899

Last Updated: 2024-02-20

Results Overview

Objective response rate (ORR) is defined as the number of patients who's best response is complete response plus those with partial response. Imaging scans will be assessed using RECIST 1.1 to measure ORR to guadecitabine and pembrolizumab in patients with recurrent platinum resistant Ovarian Cancer. In general the following definitions apply Complete Response - Disappearance of all lesions Partial Response - At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 45 participants
• Primary outcome timeframe: Assessed from start of treatment and during treatment for up to 38 cycles where 1 cycle equals 21 days (maximum number of cycles that any patient attempted)
• Results posted on: 2024-02-20

Participant Flow

The study opened to accrual May 23, 2016 with the first patient being treated on study November 14, 2016. The study was suspended January 30 2017 pending completion of safety run in and data review, reopening March 22 2017. The study closed to further accrual November 25 2019 with accrual being considered to be met.

Participant milestones

Measure	Treatment (Guadecitabine, Pembrolizumab) Patients receive guadecitabine as a subcutaneous injection on Days 1-4 and pembrolizumab as a IV infusion over 30 minutes on Day 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Reached 1st Response Assessment STARTED	45
Reached 1st Response Assessment Registered	45
Reached 1st Response Assessment Started Treatment	43
Reached 1st Response Assessment Attempted 2 Cycles of Treatment/Reached First Response	37
Reached 1st Response Assessment COMPLETED	37
Reached 1st Response Assessment NOT COMPLETED	8
Continued Treatment After 1st Response STARTED	37
Continued Treatment After 1st Response Went on to Start Cycle 3	21
Continued Treatment After 1st Response COMPLETED	21
Continued Treatment After 1st Response NOT COMPLETED	16
Follow up STARTED	43
Follow up COMPLETED	27
Follow up NOT COMPLETED	16

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Guadecitabine and Pembrolizumab in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

Baseline characteristics by cohort

Measure	Treatment (Guadecitabine, Pembrolizumab) n=45 Participants Patients receive guadecitabine as a subcutaneous injection on Days 1-4 and pembrolizumab as a IV infusion over 30 minutes on Day 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Age, Continuous	61 years n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	43 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants
Race (NIH/OMB) White	36 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Region of Enrollment United States	45 participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed from start of treatment and during treatment for up to 38 cycles where 1 cycle equals 21 days (maximum number of cycles that any patient attempted)

Population: Per protocol patients need to complete at least 2 cycles of treatment to be evaluable for this endpoint.

Objective response rate (ORR) is defined as the number of patients who's best response is complete response plus those with partial response. Imaging scans will be assessed using RECIST 1.1 to measure ORR to guadecitabine and pembrolizumab in patients with recurrent platinum resistant Ovarian Cancer.

In general the following definitions apply Complete Response - Disappearance of all lesions Partial Response - At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Measure	Treatment (Guadecitabine, Pembrolizumab) n=38 Participants Patients receive guadecitabine as a subcutaneous injection on Days 1-4 and pembrolizumab as a IV infusion over 30 minutes on Day 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Objective Response Rate (ORR) Using RECIST 1.1	3 patients

SECONDARY outcome

Timeframe: Up to 3 years

Population: This endpoint was not analyzed because the data required for analysis was not collected.

Objective response rate (ORR) is defined as the number of complete responders and partial responders divided by the patient population evaluable for response. Imaging scans will be assessed using the using the Immune Related Response Criteria (irRC) to measure ORR to guadecitabine and pembrolizumab in patients with recurrent platinum resistant Ovarian Cancer.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 3 years

Population: Only patients that completed at least 1 cycle of treatment were analyzed

Progression-Free Survival (PFS) is defined as the duration of time from treatment start to time of progression or death, whichever occurs first. The median PFS value (in months) is reported here. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Outcome measures

Measure	Treatment (Guadecitabine, Pembrolizumab) n=43 Participants Patients receive guadecitabine as a subcutaneous injection on Days 1-4 and pembrolizumab as a IV infusion over 30 minutes on Day 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Progression Free Survival (PFS)	1.74 months Interval 1.25 to 2.76

SECONDARY outcome

Timeframe: Assessed from start of treatment and during treatment for up to 38 cycles where 1 cycle equals 21 days (maximum number of cycles that any patient attempted)

Population: Patient must receive at least 2 cycles of treatment to be evaluable for this endpoint

CBR is defined as the number of patients who's best response is complete response, plus those with partial response plus those with stable disease as evaluated using imagining scans and assessed by RECIST 1.1 and received at least 6 cycles of treatment.

Complete Response - Disappearance of all lesions Partial Response - At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Stable Disease - Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of diameters while on study

Outcome measures

Measure	Treatment (Guadecitabine, Pembrolizumab) n=35 Participants Patients receive guadecitabine as a subcutaneous injection on Days 1-4 and pembrolizumab as a IV infusion over 30 minutes on Day 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Clinical Benefit Rate (CBR)	9 patients

SECONDARY outcome

Timeframe: Assessed from start of treatment and during treatment for up to 38 cycles and up to 90 days post last dose where 1 cycle equals 21 days (maximum number of cycles that any patient attempted)

Assess the toxicity of guadecitabine and pembrolizumab by measuring the number, type, grade, severity, and frequency of adverse events according to the National Cancer Institute Common Terminology Criteria Adverse events (AE) (CTCAE) v 4.03. Those that were determined to be at least possibly related to study drugs are reported per drug (guadecitabine and pembrolizumab). Number of related Serious Adverse Events (SAEs) is also reported

Outcome measures

Measure	Treatment (Guadecitabine, Pembrolizumab) n=43 Participants Patients receive guadecitabine as a subcutaneous injection on Days 1-4 and pembrolizumab as a IV infusion over 30 minutes on Day 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Incidence of Adverse Events Related to Guadecitabine : All AEs	41 participants
Incidence of Adverse Events Related to Guadecitabine : AEs graded 1-2	40 participants
Incidence of Adverse Events Related to Guadecitabine : AEs graded 3-4	23 participants
Incidence of Adverse Events Related to Guadecitabine : SAEs	3 participants
Incidence of Adverse Events Related to Pembrolizumab : All AEs	33 participants
Incidence of Adverse Events Related to Pembrolizumab : AEs graded 1-2	32 participants
Incidence of Adverse Events Related to Pembrolizumab : AEs graded 3-4	9 participants
Incidence of Adverse Events Related to Pembrolizumab : SAEs	6 participants

Adverse Events

Treatment (Guadecitabine, Pembrolizumab)

Serious events: 18 serious events

Other events: 43 other events

Deaths: 29 deaths

Serious adverse events

Measure	Treatment (Guadecitabine, Pembrolizumab) n=43 participants at risk Patients receive guadecitabine as a subcutaneous injection on Days 1-4 and pembrolizumab as a IV infusion over 30 minutes on Day 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Febrile neutropenia	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Cardiac disorders Pericardial effusion	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Abdominal pain	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Ascites	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Colitis	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Colonic obstruction	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Diarrhea	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Ileal obstruction	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Ileus	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Jejunal obstruction	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Small intestinal obstruction	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Immune system disorders Allergic reaction	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Infections and infestations Otitis media	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Infections and infestations Sepsis	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Infections and infestations Sinusitis	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Infections and infestations Skin infection	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Injury, poisoning and procedural complications Fall	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Investigations Neutrophil count decreased	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Metabolism and nutrition disorders Dehydration	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Musculoskeletal and connective tissue disorders Arthritis	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Musculoskeletal and connective tissue disorders Back pain	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	7.0% 3/43 • Number of events 3 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Renal and urinary disorders Acute kidney injury	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.7% 2/43 • Number of events 3 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Vascular disorders Thromboembolic event	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.

Other adverse events

Measure	Treatment (Guadecitabine, Pembrolizumab) n=43 participants at risk Patients receive guadecitabine as a subcutaneous injection on Days 1-4 and pembrolizumab as a IV infusion over 30 minutes on Day 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	51.2% 22/43 • Number of events 55 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Blood and lymphatic system disorders Febrile neutropenia	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Blood and lymphatic system disorders Leukocytosis	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Blood and lymphatic system disorders Lymph node pain	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Cardiac disorders Cardiac disorders - Other, specify	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Cardiac disorders Palpitations	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Cardiac disorders Sinus tachycardia	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Ear and labyrinth disorders Hearing impaired	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Endocrine disorders Endocrine disorders - Other, specify	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Endocrine disorders Hyperthyroidism	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Endocrine disorders Hypothyroidism	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Eye disorders Blurred vision	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Eye disorders Eye disorders - Other, specify	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Eye disorders Eye pain	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Eye disorders Photophobia	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Abdominal distension	14.0% 6/43 • Number of events 7 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Abdominal pain	30.2% 13/43 • Number of events 20 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Ascites	9.3% 4/43 • Number of events 5 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Bloating	14.0% 6/43 • Number of events 8 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Cheilitis	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Colitis	7.0% 3/43 • Number of events 6 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Constipation	27.9% 12/43 • Number of events 17 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Diarrhea	27.9% 12/43 • Number of events 18 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Dry mouth	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Dyspepsia	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Esophageal pain	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Flatulence	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Gastroesophageal reflux disease	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Gastrointestinal pain	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Hemorrhoids	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Ileal obstruction	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Mucositis oral	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Nausea	41.9% 18/43 • Number of events 28 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Obstruction gastric	2.3% 1/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Stomach pain	7.0% 3/43 • Number of events 3 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Gastrointestinal disorders Vomiting	25.6% 11/43 • Number of events 15 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
General disorders Chills	16.3% 7/43 • Number of events 7 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
General disorders Edema face	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
General disorders Edema limbs	7.0% 3/43 • Number of events 3 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
General disorders Fatigue	44.2% 19/43 • Number of events 22 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
General disorders Fever	16.3% 7/43 • Number of events 7 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
General disorders Flu like symptoms	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
General disorders Gait disturbance	7.0% 3/43 • Number of events 3 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
General disorders General disorders and administration site conditions - Other, specify	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
General disorders Infusion related reaction	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
General disorders Injection site reaction	27.9% 12/43 • Number of events 23 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
General disorders Irritability	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
General disorders Non-cardiac chest pain	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
General disorders Pain	4.7% 2/43 • Number of events 3 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Immune system disorders Allergic reaction	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Immune system disorders Immune system disorders - Other, specify	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Infections and infestations Anorectal infection	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Infections and infestations Device related infection	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Infections and infestations Otitis media	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Infections and infestations Rhinitis infective	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Infections and infestations Skin infection	2.3% 1/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Infections and infestations Tooth infection	7.0% 3/43 • Number of events 4 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Infections and infestations Upper respiratory infection	14.0% 6/43 • Number of events 6 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Infections and infestations Urinary tract infection	11.6% 5/43 • Number of events 6 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Injury, poisoning and procedural complications Bruising	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Injury, poisoning and procedural complications Fall	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other, specify	2.3% 1/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Investigations Activated partial thromboplastin time prolonged	9.3% 4/43 • Number of events 6 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Investigations Alanine aminotransferase increased	9.3% 4/43 • Number of events 7 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Investigations Alkaline phosphatase increased	23.3% 10/43 • Number of events 23 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Investigations Aspartate aminotransferase increased	18.6% 8/43 • Number of events 12 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Investigations Blood bilirubin increased	7.0% 3/43 • Number of events 4 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Investigations Creatinine increased	7.0% 3/43 • Number of events 5 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Investigations INR increased	7.0% 3/43 • Number of events 3 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Investigations Investigations - Other, specify	20.9% 9/43 • Number of events 13 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Investigations Lymphocyte count decreased	65.1% 28/43 • Number of events 83 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Investigations Neutrophil count decreased	53.5% 23/43 • Number of events 49 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Investigations Platelet count decreased	14.0% 6/43 • Number of events 13 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Investigations Weight loss	16.3% 7/43 • Number of events 12 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Investigations White blood cell decreased	67.4% 29/43 • Number of events 76 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Metabolism and nutrition disorders Anorexia	32.6% 14/43 • Number of events 17 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Metabolism and nutrition disorders Dehydration	7.0% 3/43 • Number of events 4 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Metabolism and nutrition disorders Hypercalcemia	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Metabolism and nutrition disorders Hyperglycemia	11.6% 5/43 • Number of events 5 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Metabolism and nutrition disorders Hyperkalemia	4.7% 2/43 • Number of events 3 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Metabolism and nutrition disorders Hyperuricemia	11.6% 5/43 • Number of events 6 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Metabolism and nutrition disorders Hypoalbuminemia	27.9% 12/43 • Number of events 28 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Metabolism and nutrition disorders Hypocalcemia	9.3% 4/43 • Number of events 6 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Metabolism and nutrition disorders Hypokalemia	18.6% 8/43 • Number of events 9 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Metabolism and nutrition disorders Hypomagnesemia	9.3% 4/43 • Number of events 5 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Metabolism and nutrition disorders Hyponatremia	18.6% 8/43 • Number of events 16 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Metabolism and nutrition disorders Hypophosphatemia	4.7% 2/43 • Number of events 4 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Metabolism and nutrition disorders Obesity	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Musculoskeletal and connective tissue disorders Arthralgia	16.3% 7/43 • Number of events 9 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Musculoskeletal and connective tissue disorders Arthritis	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Musculoskeletal and connective tissue disorders Back pain	11.6% 5/43 • Number of events 6 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Musculoskeletal and connective tissue disorders Bone pain	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Musculoskeletal and connective tissue disorders Buttock pain	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Musculoskeletal and connective tissue disorders Flank pain	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Musculoskeletal and connective tissue disorders Myalgia	11.6% 5/43 • Number of events 10 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Musculoskeletal and connective tissue disorders Neck pain	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Musculoskeletal and connective tissue disorders Pain in extremity	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Nervous system disorders Concentration impairment	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Nervous system disorders Dizziness	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Nervous system disorders Dysgeusia	4.7% 2/43 • Number of events 3 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Nervous system disorders Headache	14.0% 6/43 • Number of events 6 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Nervous system disorders Paresthesia	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Nervous system disorders Peripheral sensory neuropathy	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Nervous system disorders Presyncope	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Nervous system disorders Tremor	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Psychiatric disorders Anxiety	9.3% 4/43 • Number of events 4 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Psychiatric disorders Confusion	2.3% 1/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Psychiatric disorders Insomnia	9.3% 4/43 • Number of events 4 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Psychiatric disorders Psychiatric disorders - Other, specify	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Renal and urinary disorders Hematuria	7.0% 3/43 • Number of events 3 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Renal and urinary disorders Proteinuria	9.3% 4/43 • Number of events 5 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Renal and urinary disorders Urinary incontinence	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Renal and urinary disorders Urinary tract pain	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Renal and urinary disorders Urinary urgency	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Reproductive system and breast disorders Pelvic pain	7.0% 3/43 • Number of events 3 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Reproductive system and breast disorders Vaginal discharge	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Reproductive system and breast disorders Vaginal hemorrhage	4.7% 2/43 • Number of events 3 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Respiratory, thoracic and mediastinal disorders Atelectasis	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Respiratory, thoracic and mediastinal disorders Cough	16.3% 7/43 • Number of events 8 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Respiratory, thoracic and mediastinal disorders Dyspnea	16.3% 7/43 • Number of events 10 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Respiratory, thoracic and mediastinal disorders Hoarseness	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Respiratory, thoracic and mediastinal disorders Nasal congestion	9.3% 4/43 • Number of events 4 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Respiratory, thoracic and mediastinal disorders Pleural effusion	7.0% 3/43 • Number of events 3 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Respiratory, thoracic and mediastinal disorders Postnasal drip	7.0% 3/43 • Number of events 3 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Respiratory, thoracic and mediastinal disorders Sneezing	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Respiratory, thoracic and mediastinal disorders Sore throat	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Respiratory, thoracic and mediastinal disorders Wheezing	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Skin and subcutaneous tissue disorders Dry skin	18.6% 8/43 • Number of events 9 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Skin and subcutaneous tissue disorders Pruritus	11.6% 5/43 • Number of events 10 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Skin and subcutaneous tissue disorders Purpura	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Skin and subcutaneous tissue disorders Rash maculo-papular	9.3% 4/43 • Number of events 8 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	9.3% 4/43 • Number of events 5 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Vascular disorders Flushing	7.0% 3/43 • Number of events 3 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Vascular disorders Hot flashes	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Vascular disorders Hypertension	32.6% 14/43 • Number of events 73 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Vascular disorders Hypotension	2.3% 1/43 • Number of events 1 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.
Vascular disorders Thromboembolic event	4.7% 2/43 • Number of events 2 • Patients are assessed for adverse events (AE) from the start of the treatment, every cycle and for 30 days post last dose of treatment (up to 90 days post last dose of treatment) for up to a maximum of 38 cycles where cycles are 21 days in length, up to a total of 3 years Patients registered to the study who did not start treatment were not assessed for AEs and not included. There were a total of 29 SAEs but some contained multiple event terms. Each SAE event term is included here.

Additional Information

Daniela Matei, MD

Northwestern University

Phone: 312.472.4684

Email: daniela.matei@northwestern.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place