Trial Outcomes & Findings for A Randomised Placebo-Controlled Phase II Study of Continuous Maintenance Treatment With BIBF 1120 Following Chemotherapy in Patients With Relapsed Ovarian Cancer (NCT NCT00710762)

Last Updated: 2016-08-15

Results Overview

The rate (probability) of being progression free at Week 36. Progression Free Survival (PFS) was defined according to RECIST version 1.0 from the time of first study drug administration to the first time of either objective tumour progression, the appearance of ≥1 new tumour lesion(s), occurrence or significant progression of malignant ascites, tumour related death, or the time when patients were censored at last known follow up. The rate is the Kaplan-Meier estimated percent probability.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

89 participants

Primary outcome timeframe

36 weeks (after 9 months)

Results posted on

2016-08-15

Participant Flow

89 patients were enrolled and 84 patients were randomised for this study.

Participant milestones

Participant milestones
Measure	Nintedanib Patients were treated with 250mg nintedanib twice daily	Placebo Patients were treated with matching placebo twice daily
Overall Study STARTED	44	40
Overall Study COMPLETED	5	0
Overall Study NOT COMPLETED	39	40

Reasons for withdrawal

Reasons for withdrawal
Measure	Nintedanib Patients were treated with 250mg nintedanib twice daily	Placebo Patients were treated with matching placebo twice daily
Overall Study Progressive disease	27	30
Overall Study Adverse Event other disease worsening	2	1
Overall Study Other Adverse Event	7	7
Overall Study Lost to Follow-up	1	0
Overall Study Reason other than listed above	2	2

Baseline Characteristics

A Randomised Placebo-Controlled Phase II Study of Continuous Maintenance Treatment With BIBF 1120 Following Chemotherapy in Patients With Relapsed Ovarian Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nintedanib n=43 Participants Patients were treated with 250mg nintedanib twice daily	Placebo n=40 Participants Patients were treated with matching placebo twice daily	Total n=83 Participants Total of all reporting groups
Age, Continuous	58.4 years STANDARD_DEVIATION 9.5 • n=5 Participants	61.3 years STANDARD_DEVIATION 9.1 • n=7 Participants	59.8 years STANDARD_DEVIATION 9.3 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	40 Participants n=7 Participants	83 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 36 weeks (after 9 months)

Population: Treated set.

Outcome measures

Outcome measures
Measure	Nintedanib n=43 Participants Patients were treated with 250mg nintedanib twice daily	Placebo n=40 Participants Patients were treated with matching placebo twice daily
PFS Rate at 36 Weeks (After 9 Months)	15.6 percent probability of PFS Interval 3.8 to 27.3	2.9 percent probability of PFS Interval 0.0 to 8.4

SECONDARY outcome

Timeframe: 12 weeks (after 3 months) and 24 weeks ( after 6 months)

Population: Treated set

The rate (probability) of being progression free at Week 12 and Week 24. Progression Free Survival (PFS) was defined according to RECIST version 1.0 from the time of first study drug administration to the first time of either objective tumour progression, the appearance of ≥1 new tumour lesion(s), occurrence or significant progression of malignant ascites, tumour related death, or the time when patients were censored at last known follow up. The rate is the Kaplan-Meier estimated percent probability.

Outcome measures

Outcome measures
Measure	Nintedanib n=43 Participants Patients were treated with 250mg nintedanib twice daily	Placebo n=40 Participants Patients were treated with matching placebo twice daily
PFS Rate at 12 Weeks (After 3 Months) and 24 Weeks ( After 6 Months) at 24 weeks ( after 6 months)	26.7 percent probability of PFS Interval 12.5 to 40.8	17.3 percent probability of PFS Interval 5.2 to 29.4
PFS Rate at 12 Weeks (After 3 Months) and 24 Weeks ( After 6 Months) at 12 weeks (after 3 months)	45.3 percent probability of PFS Interval 29.5 to 61.2	46.2 percent probability of PFS Interval 30.5 to 61.8

SECONDARY outcome

Timeframe: 9 months

Population: Treated set

Time to Tumour Progression according to RECIST version 1.0 , CA-125 (ovarian tumour marker) levels and RECIST + CA-125 levels. For CA-125, progressive disease was defined on the basis of progressive serial elevations of CA-125 according to the following criteria: Patients with elevated CA-125 pre-treatment and normalisation of CA-125 had to show evidence of CA-125 levels ≥2 x ULN on 2 occasions at least 1 week apart. or Patients with elevated CA-125 pre-treatment that never normalised had to show evidence of CA-125 levels ≥2 x the nadir value on 2 occasions at least 1 week apart. or Patients with CA-125 in the normal range pre-treatment had to show evidence of CA-125 levels ≥2 x ULN on 2 occasions at least 1 week apart. Composite (RECIST+CA-125) endpoint is the RECIST progressive disease (PD) if it occurred or the CA-125 PD if it occurred in the absence of RECIST PD.

Outcome measures

Outcome measures
Measure	Nintedanib n=43 Participants Patients were treated with 250mg nintedanib twice daily	Placebo n=40 Participants Patients were treated with matching placebo twice daily
Time to Tumour Progression according to RECIST and CA-125	83.00 days Interval 78.0 to 149.0	84.00 days Interval 78.0 to 87.0
Time to Tumour Progression according to CA-125	85.00 days Interval 79.0 to 149.0	86.00 days Interval 67.0 to 113.0
Time to Tumour Progression according to RECIST	143.0 days Interval 82.0 to 175.0	85.0 days Interval 78.0 to 89.0

SECONDARY outcome

Timeframe: 9 months

Population: This endpoint could not be calculated as no patients died.

This end point was not determined as no patients died during the trial.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: First drug administration until 28 days after last drug administration,up until 309 days

Population: Treated set

Incidence and intensity of Adverse Events with grading according to the Common Terminology Criteria for Adverse Events (CTCAE version 3.0).

Outcome measures

Outcome measures
Measure	Nintedanib n=43 Participants Patients were treated with 250mg nintedanib twice daily	Placebo n=40 Participants Patients were treated with matching placebo twice daily
Incidence and Intensity of Adverse Events With Grading According CTCAE CTCAE grade 1	2.3 percentage of participants	25.0 percentage of participants
Incidence and Intensity of Adverse Events With Grading According CTCAE CTCAE grade 2	34.9 percentage of participants	42.5 percentage of participants
Incidence and Intensity of Adverse Events With Grading According CTCAE CTCAE grade 3	53.5 percentage of participants	25.0 percentage of participants
Incidence and Intensity of Adverse Events With Grading According CTCAE CTCAE grade 4	7.0 percentage of participants	2.5 percentage of participants
Incidence and Intensity of Adverse Events With Grading According CTCAE CTCAE grade 5	0.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: First drug administration until 28 days after last drug administration, up until 309 days

Population: Treated set

Clinical Relevant Abnormalities for laboratory parameters. Any new or clinically relevant worsening of baseline conditions was reported as Adverse Events.

Outcome measures

Outcome measures
Measure	Nintedanib n=43 Participants Patients were treated with 250mg nintedanib twice daily	Placebo n=40 Participants Patients were treated with matching placebo twice daily
Clinical Relevant Abnormalities for Laboratory Parameters Gamma-glutamyltransferase abnormal	2.3 Percentage of participants	0.0 Percentage of participants
Clinical Relevant Abnormalities for Laboratory Parameters Alanine aminotransferase increased	37.2 Percentage of participants	7.5 Percentage of participants
Clinical Relevant Abnormalities for Laboratory Parameters Gamma-glutamyltransferase increased	30.2 Percentage of participants	2.5 Percentage of participants
Clinical Relevant Abnormalities for Laboratory Parameters Aspartate aminotransferase increased	25.6 Percentage of participants	2.5 Percentage of participants
Clinical Relevant Abnormalities for Laboratory Parameters Blood alkaline phosphatase increased	7.0 Percentage of participants	5.0 Percentage of participants
Clinical Relevant Abnormalities for Laboratory Parameters Blood lactate dehydrogenase increased	4.7 Percentage of participants	0.0 Percentage of participants
Clinical Relevant Abnormalities for Laboratory Parameters Blood alkaline phosphatase	0.0 Percentage of participants	2.5 Percentage of participants
Clinical Relevant Abnormalities for Laboratory Parameters Blood alkaline phosphatase abnormal	2.3 Percentage of participants	2.5 Percentage of participants
Clinical Relevant Abnormalities for Laboratory Parameters Lymphocyte count decreased	0.0 Percentage of participants	2.5 Percentage of participants
Clinical Relevant Abnormalities for Laboratory Parameters Vitamin B12 decreased	0.0 Percentage of participants	2.5 Percentage of participants
Clinical Relevant Abnormalities for Laboratory Parameters Alanine aminotransferase abnormal	2.3 Percentage of participants	0.0 Percentage of participants
Clinical Relevant Abnormalities for Laboratory Parameters Blood lactate dehydrogenase abnormal	2.3 Percentage of participants	0.0 Percentage of participants
Clinical Relevant Abnormalities for Laboratory Parameters Neutrophil count decreased	2.3 Percentage of participants	0.0 Percentage of participants
Clinical Relevant Abnormalities for Laboratory Parameters White blood cells urine positive	2.3 Percentage of participants	0.0 Percentage of participants
Clinical Relevant Abnormalities for Laboratory Parameters Blood pressure increased	0.0 Percentage of participants	2.5 Percentage of participants
Clinical Relevant Abnormalities for Laboratory Parameters Electrocardiogram T wave amplitude decreased	0.0 Percentage of participants	2.5 Percentage of participants
Clinical Relevant Abnormalities for Laboratory Parameters Liver function test abnormal	2.3 Percentage of participants	0.0 Percentage of participants

Adverse Events

Nintedanib

Serious events: 14 serious events

Other events: 42 other events

Deaths: 0 deaths

Placebo

Serious events: 10 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Nintedanib n=43 participants at risk Patients were treated with 250mg nintedanib twice daily.	Placebo n=40 participants at risk Patients were treated with matching placebo twice daily.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Abdominal distension	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Abdominal pain	9.3% 4/43 • First drug administration until 28 days after last drug administration, up until 309 days	5.0% 2/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Ascites	14.0% 6/43 • First drug administration until 28 days after last drug administration, up until 309 days	12.5% 5/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Constipation	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Diarrhoea	7.0% 3/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Intestinal obstruction	4.7% 2/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Nausea	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Rectal haemorrhage	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Small intestinal obstruction	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Vomiting	23.3% 10/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
General disorders Pyrexia	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Infections and infestations Catheter related infection	0.00% 0/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Infections and infestations Lower respiratory tract infection	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Investigations Alanine aminotransferase increased	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Investigations Aspartate aminotransferase increased	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Investigations Blood alkaline phosphatase increased	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Investigations Gamma-glutamyltransferase increased	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Metabolism and nutrition disorders Anorexia	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Metabolism and nutrition disorders Dehydration	0.00% 0/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.00% 0/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine tumour	0.00% 0/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Psychiatric disorders Abnormal behaviour	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Psychiatric disorders Agitation	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Psychiatric disorders Confusional state	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Psychiatric disorders Delusion	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Psychiatric disorders Depression	0.00% 0/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Psychiatric disorders Mood altered	0.00% 0/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Respiratory, thoracic and mediastinal disorders Pleuritic pain	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Vascular disorders Deep vein thrombosis	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	0.00% 0/40 • First drug administration until 28 days after last drug administration, up until 309 days

Measure	Nintedanib n=43 participants at risk Patients were treated with 250mg nintedanib twice daily.	Placebo n=40 participants at risk Patients were treated with matching placebo twice daily.
Ear and labyrinth disorders Tinnitus	7.0% 3/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Abdominal distension	7.0% 3/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Abdominal pain	53.5% 23/43 • First drug administration until 28 days after last drug administration, up until 309 days	37.5% 15/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Constipation	20.9% 9/43 • First drug administration until 28 days after last drug administration, up until 309 days	27.5% 11/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Diarrhoea	76.7% 33/43 • First drug administration until 28 days after last drug administration, up until 309 days	35.0% 14/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Dyspepsia	7.0% 3/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Flatulence	11.6% 5/43 • First drug administration until 28 days after last drug administration, up until 309 days	10.0% 4/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Nausea	74.4% 32/43 • First drug administration until 28 days after last drug administration, up until 309 days	32.5% 13/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Rectal haemorrhage	7.0% 3/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Stomatitis	11.6% 5/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Gastrointestinal disorders Vomiting	53.5% 23/43 • First drug administration until 28 days after last drug administration, up until 309 days	22.5% 9/40 • First drug administration until 28 days after last drug administration, up until 309 days
General disorders Fatigue	27.9% 12/43 • First drug administration until 28 days after last drug administration, up until 309 days	27.5% 11/40 • First drug administration until 28 days after last drug administration, up until 309 days
General disorders Oedema peripheral	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	7.5% 3/40 • First drug administration until 28 days after last drug administration, up until 309 days
Infections and infestations Infection	7.0% 3/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Infections and infestations Nasopharyngitis	14.0% 6/43 • First drug administration until 28 days after last drug administration, up until 309 days	5.0% 2/40 • First drug administration until 28 days after last drug administration, up until 309 days
Infections and infestations Upper respiratory tract infection	9.3% 4/43 • First drug administration until 28 days after last drug administration, up until 309 days	7.5% 3/40 • First drug administration until 28 days after last drug administration, up until 309 days
Infections and infestations Urinary tract infection	9.3% 4/43 • First drug administration until 28 days after last drug administration, up until 309 days	10.0% 4/40 • First drug administration until 28 days after last drug administration, up until 309 days
Investigations Alanine aminotransferase increased	37.2% 16/43 • First drug administration until 28 days after last drug administration, up until 309 days	7.5% 3/40 • First drug administration until 28 days after last drug administration, up until 309 days
Investigations Aspartate aminotransferase increased	23.3% 10/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Investigations Gamma-glutamyltransferase increased	27.9% 12/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Metabolism and nutrition disorders Anorexia	25.6% 11/43 • First drug administration until 28 days after last drug administration, up until 309 days	15.0% 6/40 • First drug administration until 28 days after last drug administration, up until 309 days
Musculoskeletal and connective tissue disorders Arthralgia	11.6% 5/43 • First drug administration until 28 days after last drug administration, up until 309 days	15.0% 6/40 • First drug administration until 28 days after last drug administration, up until 309 days
Musculoskeletal and connective tissue disorders Back pain	4.7% 2/43 • First drug administration until 28 days after last drug administration, up until 309 days	20.0% 8/40 • First drug administration until 28 days after last drug administration, up until 309 days
Musculoskeletal and connective tissue disorders Muscle spasms	4.7% 2/43 • First drug administration until 28 days after last drug administration, up until 309 days	10.0% 4/40 • First drug administration until 28 days after last drug administration, up until 309 days
Musculoskeletal and connective tissue disorders Pain in extremity	9.3% 4/43 • First drug administration until 28 days after last drug administration, up until 309 days	5.0% 2/40 • First drug administration until 28 days after last drug administration, up until 309 days
Nervous system disorders Dizziness	9.3% 4/43 • First drug administration until 28 days after last drug administration, up until 309 days	10.0% 4/40 • First drug administration until 28 days after last drug administration, up until 309 days
Nervous system disorders Headache	14.0% 6/43 • First drug administration until 28 days after last drug administration, up until 309 days	10.0% 4/40 • First drug administration until 28 days after last drug administration, up until 309 days
Nervous system disorders Lethargy	9.3% 4/43 • First drug administration until 28 days after last drug administration, up until 309 days	10.0% 4/40 • First drug administration until 28 days after last drug administration, up until 309 days
Nervous system disorders Neuropathy peripheral	0.00% 0/43 • First drug administration until 28 days after last drug administration, up until 309 days	7.5% 3/40 • First drug administration until 28 days after last drug administration, up until 309 days
Nervous system disorders Paraesthesia	2.3% 1/43 • First drug administration until 28 days after last drug administration, up until 309 days	10.0% 4/40 • First drug administration until 28 days after last drug administration, up until 309 days
Psychiatric disorders Anxiety	4.7% 2/43 • First drug administration until 28 days after last drug administration, up until 309 days	10.0% 4/40 • First drug administration until 28 days after last drug administration, up until 309 days
Psychiatric disorders Insomnia	0.00% 0/43 • First drug administration until 28 days after last drug administration, up until 309 days	7.5% 3/40 • First drug administration until 28 days after last drug administration, up until 309 days
Respiratory, thoracic and mediastinal disorders Cough	14.0% 6/43 • First drug administration until 28 days after last drug administration, up until 309 days	2.5% 1/40 • First drug administration until 28 days after last drug administration, up until 309 days
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.6% 5/43 • First drug administration until 28 days after last drug administration, up until 309 days	7.5% 3/40 • First drug administration until 28 days after last drug administration, up until 309 days
Skin and subcutaneous tissue disorders Alopecia	4.7% 2/43 • First drug administration until 28 days after last drug administration, up until 309 days	10.0% 4/40 • First drug administration until 28 days after last drug administration, up until 309 days
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/43 • First drug administration until 28 days after last drug administration, up until 309 days	15.0% 6/40 • First drug administration until 28 days after last drug administration, up until 309 days
Skin and subcutaneous tissue disorders Rash	7.0% 3/43 • First drug administration until 28 days after last drug administration, up until 309 days	12.5% 5/40 • First drug administration until 28 days after last drug administration, up until 309 days
Vascular disorders Hot flush	7.0% 3/43 • First drug administration until 28 days after last drug administration, up until 309 days	7.5% 3/40 • First drug administration until 28 days after last drug administration, up until 309 days
Vascular disorders Hypertension	11.6% 5/43 • First drug administration until 28 days after last drug administration, up until 309 days	5.0% 2/40 • First drug administration until 28 days after last drug administration, up until 309 days