Trial Outcomes & Findings for Safety and Efficacy of RAD001 (Everolimus) in Combination With Letrozole in the Treatment of Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer (NCT NCT01231659)

Last Updated: 2021-03-26

Results Overview

Overall Response Rate (ORR) was defined as the proportion of patients whose best overall response was either complete response (CR) or partial response (PR) according to RECIST 1.0 for target lesions and assessed by CT: Complete Response (CR), disappearance of all target lesions for a period of at least one month; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (ORR) = CR + PR. Only descriptive statistics.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

72 participants

Primary outcome timeframe

From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 15 months

Results posted on

2021-03-26

Participant Flow

This study was conducted in 7 study centers in Israel.

Seventy-eight patients were planned to enroll but only 72 patients were actually enrolled and analyzed in this study.

Participant milestones

Participant milestones
Measure	Everolimus + Letrozole All patients received 2 tablets (5 mg each) of Everolimus (a total of 10 mg) + 1 tablet of Letrozole (2.5 mg) daily until disease progression or as described in the protocol.
Overall Study STARTED	72
Overall Study Per Protocol (PP) Set	72
Overall Study Safety Set	72
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	72

Reasons for withdrawal

Reasons for withdrawal
Measure	Everolimus + Letrozole All patients received 2 tablets (5 mg each) of Everolimus (a total of 10 mg) + 1 tablet of Letrozole (2.5 mg) daily until disease progression or as described in the protocol.
Overall Study Adverse Event	9
Overall Study Disease Progression	48
Overall Study Death	2
Overall Study Patient refused to complete study visit	1
Overall Study Other protocol defined criteria	12

Baseline Characteristics

Safety and Efficacy of RAD001 (Everolimus) in Combination With Letrozole in the Treatment of Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus + Letrozole n=72 Participants All patients received 2 tablets (5 mg each) of Everolimus (a total of 10 mg) + 1 tablet of Letrozole (2.5 mg) daily until disease progression or as described in the protocol.
Age, Continuous	61.7 Years STANDARD_DEVIATION 9.5 • n=93 Participants
Sex: Female, Male Female	72 Participants n=93 Participants
Sex: Female, Male Male	0 Participants n=93 Participants
Race/Ethnicity, Customized Caucasian	72 Participants n=93 Participants

PRIMARY outcome

Timeframe: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 15 months

Population: Per Protocol (PP) Set, which consisted of all patients with measurable disease at baseline, was considered. Only descriptive analysis done.

Outcome measures

Outcome measures
Measure	Everolimus + Letrozole n=43 Participants All patients received 2 tablets (5 mg each) of Everolimus (a total of 10 mg) + 1 tablet of Letrozole (2.5 mg) daily until disease progression or as described in the protocol.
Percentage of Participants With Overall Response Rate (ORR)	37.2 Percentage of Participants

SECONDARY outcome

Timeframe: Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to 66 months

Population: Per Protocol (PP) Set, which consisted of all patients with measurable disease at baseline, was considered. Only descriptive analysis done.

Progression Free Survival (PFS) was defined as the time from the date of study entry to the date of first documented tumor progression or death from any cause, whichever occurred first. If a patient did not have an event, PFS was censored at the last date of tumor assessment. For patients with measurable disease at baseline, progression was determined according to the RECIST 1.0 criteria. Only descriptive analysis done.

Outcome measures

Outcome measures
Measure	Everolimus + Letrozole n=72 Participants All patients received 2 tablets (5 mg each) of Everolimus (a total of 10 mg) + 1 tablet of Letrozole (2.5 mg) daily until disease progression or as described in the protocol.
Median Time to Progression-Free Survival (PFS)	9.0 Months Interval 0.2 to 59.6

SECONDARY outcome

Timeframe: From Date of randomization up to approximately 66 months

Population: Per Protocol (PP) Set, which consisted of all patients with measurable disease at baseline, was considered. Only descriptive analysis done.

Overall Survival (OS) was defined as the time from the date of study entry to date of death due to any cause. If a death had not observed by the date of analysis, then OS was censored at the date of last contact. Distribution of OS was estimated using the Kaplan Meier method. The median OS along with 95% CI was presented.

Outcome measures

Outcome measures
Measure	Everolimus + Letrozole n=72 Participants All patients received 2 tablets (5 mg each) of Everolimus (a total of 10 mg) + 1 tablet of Letrozole (2.5 mg) daily until disease progression or as described in the protocol.
Median Time to Overall Survival (OS)	22.3 Months Interval 0.2 to 65.0

SECONDARY outcome

Timeframe: From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 66 months

Population: Per Protocol (PP) Set, which consisted of all patients with measurable disease at baseline, was considered. Only descriptive analysis done.

Disease Control Rate (DCR) was defined as the proportion of patients whose best overall response was either: Complete Response (CR), Partial Response (PR) or Stable Disease (SD). Disease Control Rate was calculated only for patients with measurable disease at baseline and was summarized using descriptive statistics.

Outcome measures

Outcome measures
Measure	Everolimus + Letrozole n=72 Participants All patients received 2 tablets (5 mg each) of Everolimus (a total of 10 mg) + 1 tablet of Letrozole (2.5 mg) daily until disease progression or as described in the protocol.
Disease Control Rate (DCR)	85.7 Percentage of Participants Interval 74.6 to 93.3

SECONDARY outcome

Timeframe: From Date of first dose up to approximately 66 months

Population: Safety Set, which consisted of all patients who received at least 1 dose of the study medication and had at least 1 post-baseline safety evaluation, was considered. Only descriptive analysis done.

The assessment of safety was based mainly on the frequency of AEs and on the number of laboratory values that fell outside of pre-determined ranges. Other safety data (e.g. ECG, vital signs) were considered as appropriate. Only descriptive analysis done.

Outcome measures

Outcome measures
Measure	Everolimus + Letrozole n=72 Participants All patients received 2 tablets (5 mg each) of Everolimus (a total of 10 mg) + 1 tablet of Letrozole (2.5 mg) daily until disease progression or as described in the protocol.
Long-term Safety and Tolerability AEs - All	72 Participants
Long-term Safety and Tolerability AEs - Grade 3	39 Participants
Long-term Safety and Tolerability AEs - Grade 4	7 Participants

POST_HOC outcome

Timeframe: up to 2002 days (on-treatment), up to approximately 2092 days (study duration)

Population: Clinical database population (all treated patients)

On treatment deaths were collected from FPFT up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Deaths post treatment survival follow up were collected after the on- treatment period, up to approximately 2092 days. Patients who didn't die during the on-treatment period and had not stopped study participation at the time of data cut-off (end of study) were censored.

Outcome measures

Outcome measures
Measure	Everolimus + Letrozole n=72 Participants All patients received 2 tablets (5 mg each) of Everolimus (a total of 10 mg) + 1 tablet of Letrozole (2.5 mg) daily until disease progression or as described in the protocol.
All Collected Deaths On-treatment deaths	2 Participants
All Collected Deaths Post-treatment deaths	50 Participants
All Collected Deaths All deaths	52 Participants

Adverse Events

Everolimus + Letrozole

Serious events: 26 serious events

Other events: 71 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Everolimus + Letrozole n=72 participants at risk All patients received 2 tablets (5 mg each) of Everolimus (a total of 10 mg) + 1 tablet of Letrozole (2.5 mg) daily until disease progression or as described in the protocol.
Blood and lymphatic system disorders Anaemia	6.9% 5/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Cardiac disorders Cardiac arrest	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Cardiac disorders Cardiac failure congestive	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Endocrine disorders Hypercalcaemia	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Gastrointestinal disorders Nausea	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Gastrointestinal disorders Vomiting	4.2% 3/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
General disorders Death	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
General disorders Disease progression	2.8% 2/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
General disorders Infusion related reaction	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
General disorders Pyrexia	4.2% 3/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Hepatobiliary disorders Cholecystitis	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Infections and infestations Cellulitis	2.8% 2/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Infections and infestations Urinary tract infection	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Investigations Alanine aminotransferase increased	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Investigations Blood creatinine increased	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Investigations Platelet count decreased	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Musculoskeletal and connective tissue disorders Pain in extremity	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Nervous system disorders Dizziness	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Nervous system disorders Syncope	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Psychiatric disorders Confusional state	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Renal and urinary disorders Acute kidney injury	2.8% 2/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Renal and urinary disorders Hydronephrosis	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.8% 2/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Vascular disorders Angiodysplasia	1.4% 1/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.

Other adverse events

Other adverse events
Measure	Everolimus + Letrozole n=72 participants at risk All patients received 2 tablets (5 mg each) of Everolimus (a total of 10 mg) + 1 tablet of Letrozole (2.5 mg) daily until disease progression or as described in the protocol.
Respiratory, thoracic and mediastinal disorders Pneumonitis	13.9% 10/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.6% 4/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Skin and subcutaneous tissue disorders Alopecia	8.3% 6/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Skin and subcutaneous tissue disorders Dry skin	11.1% 8/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Skin and subcutaneous tissue disorders Nail ridging	11.1% 8/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Skin and subcutaneous tissue disorders Pruritus	19.4% 14/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Investigations Blood lactate dehydrogenase increased	6.9% 5/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Investigations Neutrophil count decreased	13.9% 10/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Investigations Platelet count decreased	11.1% 8/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Investigations Weight decreased	29.2% 21/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Investigations White blood cell count decreased	8.3% 6/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Metabolism and nutrition disorders Decreased appetite	33.3% 24/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Metabolism and nutrition disorders Hyperglycaemia	26.4% 19/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Metabolism and nutrition disorders Hypertriglyceridaemia	6.9% 5/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Metabolism and nutrition disorders Hypokalaemia	9.7% 7/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Musculoskeletal and connective tissue disorders Arthralgia	16.7% 12/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Musculoskeletal and connective tissue disorders Back pain	16.7% 12/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Musculoskeletal and connective tissue disorders Bone pain	5.6% 4/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	11.1% 8/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	8.3% 6/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Musculoskeletal and connective tissue disorders Myalgia	9.7% 7/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Musculoskeletal and connective tissue disorders Pain in extremity	19.4% 14/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Nervous system disorders Dizziness	13.9% 10/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Nervous system disorders Dysgeusia	20.8% 15/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Nervous system disorders Headache	30.6% 22/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Psychiatric disorders Insomnia	11.1% 8/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Reproductive system and breast disorders Pelvic pain	6.9% 5/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Respiratory, thoracic and mediastinal disorders Cough	31.9% 23/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Respiratory, thoracic and mediastinal disorders Dysphonia	11.1% 8/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Respiratory, thoracic and mediastinal disorders Dyspnoea	23.6% 17/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Respiratory, thoracic and mediastinal disorders Epistaxis	20.8% 15/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	11.1% 8/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Blood and lymphatic system disorders Anaemia	29.2% 21/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Blood and lymphatic system disorders Neutropenia	5.6% 4/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Blood and lymphatic system disorders Thrombocytopenia	6.9% 5/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Gastrointestinal disorders Abdominal pain	19.4% 14/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Gastrointestinal disorders Abdominal pain upper	6.9% 5/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Gastrointestinal disorders Constipation	11.1% 8/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Gastrointestinal disorders Diarrhoea	29.2% 21/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Gastrointestinal disorders Dry mouth	12.5% 9/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Gastrointestinal disorders Gingival pain	8.3% 6/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Gastrointestinal disorders Nausea	20.8% 15/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Gastrointestinal disorders Oral pain	5.6% 4/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Gastrointestinal disorders Stomatitis	37.5% 27/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Gastrointestinal disorders Toothache	5.6% 4/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Gastrointestinal disorders Vomiting	12.5% 9/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
General disorders Asthenia	6.9% 5/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
General disorders Chest pain	5.6% 4/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
General disorders Disease progression	22.2% 16/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
General disorders Fatigue	68.1% 49/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
General disorders Influenza like illness	25.0% 18/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
General disorders Local swelling	5.6% 4/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
General disorders Mucosal inflammation	31.9% 23/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
General disorders Oedema peripheral	25.0% 18/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
General disorders Pyrexia	22.2% 16/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Infections and infestations Pharyngitis	5.6% 4/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Infections and infestations Sinusitis	6.9% 5/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Infections and infestations Urinary tract infection	15.3% 11/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Infections and infestations Viral infection	5.6% 4/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Injury, poisoning and procedural complications Fall	8.3% 6/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Investigations Alanine aminotransferase increased	5.6% 4/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Investigations Blood cholesterol increased	13.9% 10/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Investigations Blood creatinine increased	5.6% 4/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Skin and subcutaneous tissue disorders Rash	30.6% 22/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.6% 4/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Vascular disorders Hot flush	5.6% 4/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Vascular disorders Hypertension	11.1% 8/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.
Vascular disorders Lymphoedema	6.9% 5/72 • Adverse Events were collected from First Patient First Treatment (FPFT) up to 28 days after study drug discontinuation, for a maximum duration of 2002 days (treatment duration ranged from 1 to 1974 days). Any sign or symptom that occurs during the study treatment and 28 days post treatment follow up.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER