Trial Outcomes & Findings for Provenge With or Without pTVG-HP DNA Booster Vaccine in Prostate Cancer (NCT NCT01706458)

Last Updated: 2021-06-18

Results Overview

The primary immunological goal of this study was to determine whether booster immunizations with a DNA vaccine encoding PAP could augment the number of PAP-specific effector and memory T cells following treatment with sipuleucel-T, or prolong the duration of detectable T-cell response. All subjects received a tetanus booster immunization prior to beginning the immunization series, providing a separate test of an individual's immune responsiveness. Responses to PSA, a non-target prostate specific protein, were concurrently evaluated, as were responses to GM-CSF, a component of the PA2024 fusion protein used in the preparation of sipuleucel-T.Samples were evaluated for antigen-specific IFNy or granzyme B secretion by ELISPOT, and the detection of statistically significant antigen-specific responses, that were at least 3-fold over the baseline value, and detectable more than once post-treatment, were used to define immune response to a particular antigen.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

18 participants

Primary outcome timeframe

12 months

Results posted on

2021-06-18

Participant Flow

Participant milestones

Participant milestones
Measure	Sipuleucel-T Patients receive sipuleucel-T IV on weeks 0, 2, and 4. sipuleucel-T: Given IV	Sipuleucel-T With DNA Vaccine Patients receive sipuleucel-T as patients in arm I and pTVG-HP plasmid DNA vaccine ID on weeks 6, 8, 10, and 12, and then at 6 and 9 months. sipuleucel-T: Given IV DNA Vaccine: Given ID
Overall Study STARTED	9	9
Overall Study COMPLETED	6	5
Overall Study NOT COMPLETED	3	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Sipuleucel-T Patients receive sipuleucel-T IV on weeks 0, 2, and 4. sipuleucel-T: Given IV	Sipuleucel-T With DNA Vaccine Patients receive sipuleucel-T as patients in arm I and pTVG-HP plasmid DNA vaccine ID on weeks 6, 8, 10, and 12, and then at 6 and 9 months. sipuleucel-T: Given IV DNA Vaccine: Given ID
Overall Study Physician Decision	3	4

Baseline Characteristics

Provenge With or Without pTVG-HP DNA Booster Vaccine in Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sipuleucel-T n=9 Participants Patients receive sipuleucel-T IV on weeks 0, 2, and 4. sipuleucel-T: Given IV	Sipuleucel-T With DNA Vaccine n=9 Participants Patients receive sipuleucel-T as patients in arm I and pTVG-HP plasmid DNA vaccine ID on weeks 6, 8, 10, and 12, and then at 6 and 9 months. sipuleucel-T: Given IV DNA Vaccine: Given ID	Total n=18 Participants Total of all reporting groups
Age, Continuous	75 years n=5 Participants	72 years n=7 Participants	74 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	9 Participants n=7 Participants	18 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
ECOG Performance Status 0	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
ECOG Performance Status 1	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Gleason score < 7	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Gleason score 7	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Gleason score 8	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Gleason score >/= 9	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Gleason score Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Metastatic sites Visceral	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Metastatic sites Bone	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Metastatic sites Distant lymph nodes	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Baseline PSA (ng/mL)	32.6 ng/mL n=5 Participants	11.2 ng/mL n=7 Participants	16.25 ng/mL n=5 Participants
Baseline PSA doubling time (months)	2.8 months n=5 Participants	2.2 months n=7 Participants	2.55 months n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Outcome measures

Outcome measures
Measure	Sipuleucel-T n=9 Participants Patients receive sipuleucel-T IV on weeks 0, 2, and 4. sipuleucel-T: Given IV	Sipuleucel-T With DNA Vaccine n=9 Participants Patients receive sipuleucel-T as patients in arm I and pTVG-HP plasmid DNA vaccine ID on weeks 6, 8, 10, and 12, and then at 6 and 9 months. sipuleucel-T: Given IV DNA Vaccine: Given ID
Number of Participants With Immune Response Following Treatment	6 Participants	5 Participants

SECONDARY outcome

Timeframe: 12 months

Percentage of patients without radiographic progression at 12 months.

Outcome measures

Outcome measures
Measure	Sipuleucel-T n=9 Participants Patients receive sipuleucel-T IV on weeks 0, 2, and 4. sipuleucel-T: Given IV	Sipuleucel-T With DNA Vaccine n=9 Participants Patients receive sipuleucel-T as patients in arm I and pTVG-HP plasmid DNA vaccine ID on weeks 6, 8, 10, and 12, and then at 6 and 9 months. sipuleucel-T: Given IV DNA Vaccine: Given ID
Progression-free Survival	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Time to radiographic progression using staging obtained at month 3 as baseline for evaluation.

Outcome measures

Outcome measures
Measure	Sipuleucel-T n=9 Participants Patients receive sipuleucel-T IV on weeks 0, 2, and 4. sipuleucel-T: Given IV	Sipuleucel-T With DNA Vaccine n=9 Participants Patients receive sipuleucel-T as patients in arm I and pTVG-HP plasmid DNA vaccine ID on weeks 6, 8, 10, and 12, and then at 6 and 9 months. sipuleucel-T: Given IV DNA Vaccine: Given ID
Time to Radiographic Disease Progression	161 days Interval 85.0 to 259.0	164 days Interval 85.0 to 343.0

SECONDARY outcome

Timeframe: 12 months

PSA doubling times were calculated from PSA values obtained up to 6 months from day 1 of study treatment. An increase in the PSA doubling time to at least double the baseline value will be defined as a PSA doubling time "response".

Outcome measures

Outcome measures
Measure	Sipuleucel-T n=9 Participants Patients receive sipuleucel-T IV on weeks 0, 2, and 4. sipuleucel-T: Given IV	Sipuleucel-T With DNA Vaccine n=9 Participants Patients receive sipuleucel-T as patients in arm I and pTVG-HP plasmid DNA vaccine ID on weeks 6, 8, 10, and 12, and then at 6 and 9 months. sipuleucel-T: Given IV DNA Vaccine: Given ID
Measure Prostate-specific Antigen (PSA) Doubling Time	2.5 months Interval 1.1 to 8.8	2.6 months Interval 1.7 to 3.6

OTHER_PRE_SPECIFIED outcome

Timeframe: up to approximately 5 years

Overall survival is defined as the time interval from randomization to death from any cause or to the last follow-up in censored patients.

Outcome measures

Outcome measures
Measure	Sipuleucel-T n=9 Participants Patients receive sipuleucel-T IV on weeks 0, 2, and 4. sipuleucel-T: Given IV	Sipuleucel-T With DNA Vaccine n=9 Participants Patients receive sipuleucel-T as patients in arm I and pTVG-HP plasmid DNA vaccine ID on weeks 6, 8, 10, and 12, and then at 6 and 9 months. sipuleucel-T: Given IV DNA Vaccine: Given ID
Overall Survival: Median Time to Death From Any Cause	32.3 months Interval 7.7 to 66.7	29.6 months Interval 14.6 to 46.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 months

Population: This outcome measure was not determined because there was no progression free survival at one-year.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

A response resulting from immunization was defined as a PAP-specific response detectable more than once post-treatment that was both significant (compared to media only control), at least 3-fold higher than the pre-treatment value, and with a frequency\> 1:100,000 PBMC. An antibody response was defined as any increase in titer over baseline.

Outcome measures

Outcome measures
Measure	Sipuleucel-T n=9 Participants Patients receive sipuleucel-T IV on weeks 0, 2, and 4. sipuleucel-T: Given IV	Sipuleucel-T With DNA Vaccine n=9 Participants Patients receive sipuleucel-T as patients in arm I and pTVG-HP plasmid DNA vaccine ID on weeks 6, 8, 10, and 12, and then at 6 and 9 months. sipuleucel-T: Given IV DNA Vaccine: Given ID
PAP-specific Antibody and T-cell Immune Responses Following Treatment With Sipuleucel-T and DNA Vaccine Interferon Gamma Response	3 Participants	2 Participants
PAP-specific Antibody and T-cell Immune Responses Following Treatment With Sipuleucel-T and DNA Vaccine Granzyme B	4 Participants	4 Participants
PAP-specific Antibody and T-cell Immune Responses Following Treatment With Sipuleucel-T and DNA Vaccine Antibody Response	3 Participants	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Population: This outcome measure was not determined because there was no progression free survival at one-year.

Not performed because no progression free survival at one year.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Population: This outcome measure was not determined because there was no progression-free survival at one-year.

Not performed because no progression free survival at one year.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 12 months

Population: This outcome measure was not determined because there was no progression free survival at one-year.

Not performed because no progression free survival at one year.

Outcome measures

Outcome data not reported

Adverse Events

Sipuleucel-T

Serious events: 1 serious events

Other events: 9 other events

Deaths: 5 deaths

Sipuleucel-T With DNA Vaccine

Serious events: 2 serious events

Other events: 9 other events

Deaths: 8 deaths

Serious adverse events

Serious adverse events
Measure	Sipuleucel-T n=9 participants at risk Patients receive sipuleucel-T IV on weeks 0, 2, and 4. sipuleucel-T: Given IV	Sipuleucel-T With DNA Vaccine n=9 participants at risk Patients receive sipuleucel-T as patients in arm I and pTVG-HP plasmid DNA vaccine ID on weeks 6, 8, 10, and 12, and then at 6 and 9 months. sipuleucel-T: Given IV DNA Vaccine: Given ID
Renal and urinary disorders Urinary tract obstruction	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.
Injury, poisoning and procedural complications Fall	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Injury, poisoning and procedural complications Fracture	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Surgical and medical procedures Surgical and medical procedures - Other, specify	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Vascular disorders Hematoma	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.

Other adverse events

Additional Information

Mary Jane Staab - Program Manager

UWCCC

Phone: 608-262-4304

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Sipuleucel-T n=9 participants at risk Patients receive sipuleucel-T IV on weeks 0, 2, and 4. sipuleucel-T: Given IV	Sipuleucel-T With DNA Vaccine n=9 participants at risk Patients receive sipuleucel-T as patients in arm I and pTVG-HP plasmid DNA vaccine ID on weeks 6, 8, 10, and 12, and then at 6 and 9 months. sipuleucel-T: Given IV DNA Vaccine: Given ID
Blood and lymphatic system disorders Anemia	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Gastrointestinal disorders Nausea	11.1% 1/9 • Number of events 3 • Overall, patients were followed for a mean of 24 months.	44.4% 4/9 • Number of events 4 • Overall, patients were followed for a mean of 24 months.
Gastrointestinal disorders Abdominal Pain	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Gastrointestinal disorders Constipation	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Gastrointestinal disorders Diarrhea	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 3 • Overall, patients were followed for a mean of 24 months.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Gastrointestinal disorders Vomiting	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
General disorders Chills	33.3% 3/9 • Number of events 3 • Overall, patients were followed for a mean of 24 months.	22.2% 2/9 • Number of events 2 • Overall, patients were followed for a mean of 24 months.
General disorders Fatigue	33.3% 3/9 • Number of events 3 • Overall, patients were followed for a mean of 24 months.	33.3% 3/9 • Number of events 5 • Overall, patients were followed for a mean of 24 months.
General disorders Fever	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
General disorders Non-cardiac chest pain	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.
General disorders Injection site reaction	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	44.4% 4/9 • Number of events 6 • Overall, patients were followed for a mean of 24 months.
General disorders Localized edema	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
General disorders Malaise	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	22.2% 2/9 • Number of events 2 • Overall, patients were followed for a mean of 24 months.
General disorders Pain	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 3 • Overall, patients were followed for a mean of 24 months.
Infections and infestations Sinusitis	22.2% 2/9 • Number of events 2 • Overall, patients were followed for a mean of 24 months.	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.
Infections and infestations Tooth infection	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Injury, poisoning and procedural complications Fall	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Injury, poisoning and procedural complications Fracture	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Investigations White blood cell decreased	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Investigations Alkaline phosphatase increased	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	22.2% 2/9 • Number of events 2 • Overall, patients were followed for a mean of 24 months.
Investigations Platelet count decreased	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Metabolism and nutrition disorders Anorexia	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.	22.2% 2/9 • Number of events 2 • Overall, patients were followed for a mean of 24 months.
Metabolism and nutrition disorders Dehydration	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Musculoskeletal and connective tissue disorders Back pain	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.	44.4% 4/9 • Number of events 4 • Overall, patients were followed for a mean of 24 months.
Musculoskeletal and connective tissue disorders Bone pain	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.	22.2% 2/9 • Number of events 2 • Overall, patients were followed for a mean of 24 months.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	22.2% 2/9 • Number of events 2 • Overall, patients were followed for a mean of 24 months.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	22.2% 2/9 • Number of events 3 • Overall, patients were followed for a mean of 24 months.
Nervous system disorders Heahache	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	33.3% 3/9 • Number of events 3 • Overall, patients were followed for a mean of 24 months.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Nervous system disorders Presyncope	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 2 • Overall, patients were followed for a mean of 24 months.
Nervous system disorders Vasovagal reaction	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Psychiatric disorders Insomnia	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.
Renal and urinary disorders Urinary tract obstruction	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.
Reproductive system and breast disorders Pelvic pain	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Reproductive system and breast disorders Testicular pain	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Respiratory, thoracic and mediastinal disorders Cough	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	11.1% 1/9 • Number of events 2 • Overall, patients were followed for a mean of 24 months.	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.
Respiratory, thoracic and mediastinal disorders Postnasal drip	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.
Respiratory, thoracic and mediastinal disorders Hoarseness	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.
Surgical and medical procedures Surgical and medical procedures - Other, specify	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Vascular disorders Hematoma	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Vascular disorders Hypertension	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.
Vascular disorders Hot flashes	0.00% 0/9 • Overall, patients were followed for a mean of 24 months.	11.1% 1/9 • Number of events 1 • Overall, patients were followed for a mean of 24 months.