Trial Outcomes & Findings for Everolimus Versus Sunitinib in Non-Clear Cell Renal Cell Carcinoma (NCT NCT01185366)

Last Updated: 2021-04-28

Results Overview

The amount of time after the first line medication begins until the cancer gets worse progresses. Progression is measured by an increase in measures tumors of at least 20 %, or overall increase in all the tumors, or the presence of new tumors.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

73 participants

Primary outcome timeframe

7 months

Results posted on

2021-04-28

Participant Flow

73 Participants recruited from August 2010 to November 2013 at MD Anderson and Dana-Farber/Harvard Cancer Center.

73 participants were recruited, 1 Screen failure. 69 participants were evaluable. Eligible patients did not take systemic medication for advanced papillary, chromophobe, CDC, Xp11.2 translocation, unclassified RCC or ccRCC with ≥ 20% sarcomatoid features in their primary tumors.

Participant milestones

Participant milestones
Measure	Everolimus 4 weeks of everolimus of 10 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to sunitinib.	Sunitinib 4 weeks of sunitinib of 50 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to everolimus.
First Line Therapy STARTED	38	34
First Line Therapy Received 1st Drug	36	33
First Line Therapy COMPLETED	35	33
First Line Therapy NOT COMPLETED	3	1
Crossover to Second Line Therapy STARTED	35	33
Crossover to Second Line Therapy Received Crossover Drug	21	23
Crossover to Second Line Therapy COMPLETED	21	23
Crossover to Second Line Therapy NOT COMPLETED	14	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Everolimus 4 weeks of everolimus of 10 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to sunitinib.	Sunitinib 4 weeks of sunitinib of 50 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to everolimus.
First Line Therapy Insurance Coverage Denied	1	1
First Line Therapy Withdrawal by Subject	1	0
First Line Therapy Lack of Metastatic Site	1	0
Crossover to Second Line Therapy Adverse Event	3	6
Crossover to Second Line Therapy Physician Decision	5	1
Crossover to Second Line Therapy Withdrawal by Subject	1	0
Crossover to Second Line Therapy Continued with 1st drug	5	3

Baseline Characteristics

Everolimus Versus Sunitinib in Non-Clear Cell Renal Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus n=35 Participants 4 weeks of everolimus of 10 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to sunitinib.	Sunitinib n=33 Participants 4 weeks of sunitinib of 50 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to everolimus.	Total n=68 Participants Total of all reporting groups
Age, Continuous	58 years n=5 Participants	60 years n=7 Participants	60 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	14 Participants n=7 Participants	25 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	19 Participants n=7 Participants	43 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	29 Participants n=5 Participants	25 Participants n=7 Participants	54 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	28 Participants n=5 Participants	25 Participants n=7 Participants	53 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	05 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment United States	35 Participants n=5 Participants	33 Participants n=7 Participants	68 Participants n=5 Participants
Histology Papillary	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Histology Clear Cell with sarcomatoid features	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Histology Chromophobe	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Histology Translocation	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Histology Unclassified	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
ECOG Performance Score 0	15 participants n=5 Participants	18 participants n=7 Participants	33 participants n=5 Participants
ECOG Performance Score 1	20 participants n=5 Participants	15 participants n=7 Participants	35 participants n=5 Participants
ECOG Performance Score 2	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
ECOG Performance Score 3	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
ECOG Performance Score 4	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
ECOG Performance Score 5	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Memorial Sloan Kettering Risk Group Good	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
Memorial Sloan Kettering Risk Group Intermediate	29 participants n=5 Participants	29 participants n=7 Participants	58 participants n=5 Participants
Memorial Sloan Kettering Risk Group Poor	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
International Metastatic RCC Database Consortium Risk Score for Renal Cell Carcinoma (RCC) Good	4 participants n=5 Participants	3 participants n=7 Participants	7 participants n=5 Participants
International Metastatic RCC Database Consortium Risk Score for Renal Cell Carcinoma (RCC) Intermediate	24 participants n=5 Participants	26 participants n=7 Participants	50 participants n=5 Participants
International Metastatic RCC Database Consortium Risk Score for Renal Cell Carcinoma (RCC) Poor	7 participants n=5 Participants	4 participants n=7 Participants	11 participants n=5 Participants

PRIMARY outcome

Timeframe: 7 months

Outcome measures

Outcome measures
Measure	Everolimus n=35 Participants 4 weeks of everolimus of 10 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to sunitinib.	Sunitinib n=33 Participants 4 weeks of sunitinib of 50 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to everolimus.
Progression Free Survival (PFS) for First Line Medication	4.1 months Interval 2.7 to 10.5	6.1 months Interval 4.2 to 9.4

PRIMARY outcome

Timeframe: 4 months

The amount of time after the crossover medication begins until the cancer gets worse progresses. Progression is measured by an increase in measures tumors of at least 20 %, or overall increase in all the tumors, or the presence of new tumors.

Outcome measures

Outcome measures
Measure	Everolimus n=21 Participants 4 weeks of everolimus of 10 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to sunitinib.	Sunitinib n=23 Participants 4 weeks of sunitinib of 50 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to everolimus.
Progression Free Survival (PFS) for Crossover Medication	1.8 months Interval 1.4 to 10.6	1.8 months Interval 1.4 to insufficient number of participants with events

SECONDARY outcome

Timeframe: 1 year

Side effects, also called adverse events, that were related to either drug were documented and graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3. Grades increases in severity from 1 - 5. Grade one is a mild change which only requires monitoring. Grade 2 is a moderate change and may require some medication. Grade 3 is severe and requires hospitalization. Grade 4 is life threatening. Grade 5 is death.

Outcome measures

Outcome measures
Measure	Everolimus n=57 Participants 4 weeks of everolimus of 10 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to sunitinib.	Sunitinib n=51 Participants 4 weeks of sunitinib of 50 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to everolimus.
Number of Participants Who Experienced Either a Grade 3 or 4 Adverse Event	18 Participants	27 Participants

SECONDARY outcome

Timeframe: 17 months

The amount of time each participant is alive from the start of the first line therapy.

Outcome measures

Outcome measures
Measure	Everolimus n=35 Participants 4 weeks of everolimus of 10 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to sunitinib.	Sunitinib n=33 Participants 4 weeks of sunitinib of 50 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to everolimus.
Overall Survival of the First Line Therapy	14.9 months Interval 8.0 to 23.4	16.2 months Interval 14.2 to insufficient number of participants with events

SECONDARY outcome

Timeframe: 7 months

The best overall response for each participant was determined by using the Response Evaluation Criteria for Solid Tumors (RECIST). The responses are Complete Response (CR), Partial Response (PR), Stable Disease (SD), and Progression Disease (PD). CR is the disappearance of the cancer everywhere in the participant. PR is at least a 30 % reduction in the measured tumors from baseline. SD is no discernible change in the presence of cancer. Progressive disease is an increase of at least 20% of the measured cancer from the cancer's smallest measure.

Outcome measures

Outcome measures
Measure	Everolimus n=35 Participants 4 weeks of everolimus of 10 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to sunitinib.	Sunitinib n=33 Participants 4 weeks of sunitinib of 50 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to everolimus.
Number of Participants With Best Overall Response for First Line Medication Partial Response	1 Participants	3 Participants
Number of Participants With Best Overall Response for First Line Medication Stable Disease	26 Participants	21 Participants
Number of Participants With Best Overall Response for First Line Medication Complete Response	0 Participants	0 Participants
Number of Participants With Best Overall Response for First Line Medication Progressive Disease	8 Participants	9 Participants

Adverse Events

Everolimus

Serious events: 12 serious events

Other events: 38 other events

Deaths: 21 deaths

Sunitinib

Serious events: 14 serious events

Other events: 46 other events

Deaths: 20 deaths

Serious adverse events

Other adverse events

Additional Information

Amado Zurita-Saavedra,Associate Professor, Genitourinary Medical Oncology

UT MD Anderson Cancer Center

Phone: (713) 563-6966

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Everolimus n=57 participants at risk 4 weeks of everolimus 10 mg orally each day then 2 weeks of no medication until progression.	Sunitinib n=51 participants at risk 4 weeks of sunitinib 50 mg orally each day then 2 weeks of no medication until progression. At progression will crossover to everolimus.
Renal and urinary disorders Creatinine	0.00% 0/57 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.	2.0% 1/51 • Number of events 1 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.
Musculoskeletal and connective tissue disorders Muscle Weakness	0.00% 0/57 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.	2.0% 1/51 • Number of events 1 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.
Immune system disorders Platelets	0.00% 0/57 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.	5.9% 3/51 • Number of events 3 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.
Renal and urinary disorders Renal Failure	0.00% 0/57 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.	2.0% 1/51 • Number of events 1 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.
Gastrointestinal disorders Diarrhea	1.8% 1/57 • Number of events 1 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.	2.0% 1/51 • Number of events 1 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.
Nervous system disorders Pain	1.8% 1/57 • Number of events 1 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.	3.9% 2/51 • Number of events 2 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.
Skin and subcutaneous tissue disorders Rash	0.00% 0/57 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.	2.0% 1/51 • Number of events 1 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.
Investigations Hyponatremia	0.00% 0/57 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.	3.9% 2/51 • Number of events 2 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.
Vascular disorders Thrombosis	0.00% 0/57 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.	2.0% 1/51 • Number of events 1 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.
Gastrointestinal disorders Constipation	1.8% 1/57 • Number of events 1 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.	0.00% 0/51 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.
Infections and infestations Kidney Infection	1.8% 1/57 • Number of events 1 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.	0.00% 0/51 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.
Blood and lymphatic system disorders CNS cerebrovascular ischemia	1.8% 1/57 • Number of events 1 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.	0.00% 0/51 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.
Respiratory, thoracic and mediastinal disorders Dyspnea	8.8% 5/57 • Number of events 5 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.	0.00% 0/51 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.
Infections and infestations Infection	3.5% 2/57 • Number of events 2 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.	0.00% 0/51 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.
Gastrointestinal disorders Vomiting	1.8% 1/57 • Number of events 1 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.	0.00% 0/51 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.
Blood and lymphatic system disorders Hemorrhage	1.8% 1/57 • Number of events 1 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.	5.9% 3/51 • Number of events 3 • All Cause Mortality was measure for 8 Years. Adverse events and Serious adverse events were measured for 1 year. Adverse events that were related to either medication were documented and graded for severity according to the Common Terminology Criteria of Adverse Events (CTCAE) version 3. Grades increase in severity from 1 - 5. Grade 1 is a mild change. Grade 2 is a moderate change. Grade 3 is a sever change and may require hospitalization. Grade 4 is life threatening. Grade 5 is death.