Trial Outcomes & Findings for Rheumatological Evaluation of Anastrozole and Letrozole as Adjuvant Treatment in Post-menopausal Women With Breast Cancer (NCT NCT00688909)

NCT ID: NCT00688909

Last Updated: 2021-06-09

Results Overview

The arthralgia status and the myalgia status were separately graded at Baseline (V1), Week 12 (V3) , and Week 24/EOS (V4). The grades of 0 for no pain, 1 for mild pain, 2 for moderate pain, 3 for severe pain, and 4 for disabling pain were used.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 261 participants
• Primary outcome timeframe: End of Study (24 weeks)
• Results posted on: 2021-06-09

Participant Flow

The study enrolled 261 participants at 45 centers in United States.

It was estimated it would be necessary to enroll 228 patients so that the percentage of patients discontinuing due to arthralgia-myalgias would be 50%, within 6.5% of the true percentage with 95% confidence.

Participant milestones

Measure	Letrozole Participants received 2.5 milligram (mg) of Letrozole tablets orally once daily (QD) for a period of 24 weeks.
Overall Study STARTED	261
Overall Study COMPLETED	228
Overall Study NOT COMPLETED	33

Reasons for withdrawal

Measure	Letrozole Participants received 2.5 milligram (mg) of Letrozole tablets orally once daily (QD) for a period of 24 weeks.
Overall Study Adverse Event	28
Overall Study Patient withdrew consent	2
Overall Study Administrative problems	1
Overall Study Protocol Violation	2

Baseline Characteristics

Rheumatological Evaluation of Anastrozole and Letrozole as Adjuvant Treatment in Post-menopausal Women With Breast Cancer

Baseline characteristics by cohort

Measure	Letrozole n=261 Participants Participants received 2.5 milligram (mg) of Letrozole tablets orally once daily (QD) for a period of 24 weeks.
Age, Continuous	61.6 years STANDARD_DEVIATION 10.2 • n=93 Participants
Sex/Gender, Customized Female	261 Participants n=93 Participants
Race/Ethnicity, Customized Caucasian	235 Participants n=93 Participants
Race/Ethnicity, Customized Black	14 Participants n=93 Participants
Race/Ethnicity, Customized Asian	3 Participants n=93 Participants
Race/Ethnicity, Customized Other	9 Participants n=93 Participants
Relevant Medical and Surgical History Yes	261 Participants n=93 Participants
Relevant Medical and Surgical History No	0 Participants n=93 Participants
Rheumatology History Yes	261 Participants n=93 Participants
Rheumatology History No	0 Participants n=93 Participants

PRIMARY outcome

Timeframe: End of Study (24 weeks)

Population: Safety set: All participants who received at least one dose of study drug.

The arthralgia status and the myalgia status were separately graded at Baseline (V1), Week 12 (V3) , and Week 24/EOS (V4). The grades of 0 for no pain, 1 for mild pain, 2 for moderate pain, 3 for severe pain, and 4 for disabling pain were used.

Outcome measures

Measure	Letrozole n=261 Participants Participants received 2.5 milligram (mg) of Letrozole tablets orally once daily (QD) for a period of 24 weeks.
Number of Participants Discontinuing Due to Grade 2 or Higher Arthralgia-myalgia.	25 Participants

SECONDARY outcome

Timeframe: End of Study (24 weeks)

Population: Safety set: All participants who received at least one dose of study drug.

For patients who discontinued from the study due to either grade 2 or higher arthralgia-myalgia, the time to discontinuation was calculated as the duration between the Visit 1 date and the last dose date. If the last dose date was missing, the EOS date was used.

Outcome measures

Measure	Letrozole n=261 Participants Participants received 2.5 milligram (mg) of Letrozole tablets orally once daily (QD) for a period of 24 weeks.
Time to Discontinuation Due to Grade 2 or Higher Arthralgia- Myalgia.	156.98 days Standard Error 1.94

SECONDARY outcome

Timeframe: End of Study (24 weeks)

Population: Safety set: All participants who received at least one dose of study drug.

The percentage of patients who discontinued from the study irrespective of the reasons.

Outcome measures

Measure	Letrozole n=261 Participants Participants received 2.5 milligram (mg) of Letrozole tablets orally once daily (QD) for a period of 24 weeks.
Percentage of Participants Discontinuing, Irrespective of Cause	33 Participants

SECONDARY outcome

Timeframe: Baseline, 24 weeks (End of Study)

Population: Safety set: All participants who received at least one dose of study drug.

The BPI is a pain assessment tool for use with cancer patients. The BPI measures both the intensity of pain (sensory dimension) and interference of pain in the patient's life (reactive dimension). It also queries the patient about pain relief, pain quality, and patient perception of the cause of pain. The BPI composite score was calculated based on questions 3 to 6 of the BPI Questionnaire (short form). First each question was scored from 0 (no pain) to 10 (pain as bad as you can imagine) and circled on the CRF. Then a composite score was calculated as the mean of the scores. If any answer was missing, the composite score was set to missing. Change in BPI composite score indicates the change from baseline at week 24.

Outcome measures

Measure	Letrozole n=261 Participants Participants received 2.5 milligram (mg) of Letrozole tablets orally once daily (QD) for a period of 24 weeks.
Change in Brief Pain Inventory (BPI) Composite Score Baseline visit	2.78 score on a scale Standard Deviation 2.00
Change in Brief Pain Inventory (BPI) Composite Score Week 24	-0.46 score on a scale Standard Deviation 2.09

SECONDARY outcome

Timeframe: Baseline, Visit 1(24 weeks = End of Study)

Population: Safety set: All participants who received at least one dose of study drug.

The HAQ is a validated, patient-oriented outcome assessment instrument. The short version '2 page HAQ' was used. It contains the HAQ Disability Index (HAQ-DI), the HAQ visual analog scale (VAS) for pain and the VAS patient global health scale. The Stanford HAQ 20-item disability scale was utilized for scoring of the Disability Index. The items were first scored within each category with values 0 to 3 (0 = Without any difficulty, 1 = With some difficulty, 2 = With much difficulty, 3 = Unable to do). The score for the disability index was the mean of the eight category scores. If more than 2 of the 8 categories, or >25%, were missing, the scale was not scored. If ≤2 of the categories were missing, the sum of the categories was divided by the number of answered categories. Change in Disability Index indicates the change from baseline at week 24.

Outcome measures

Measure	Letrozole n=261 Participants Participants received 2.5 milligram (mg) of Letrozole tablets orally once daily (QD) for a period of 24 weeks.
Change in Disability Index as Assessed by Health Assessment Questionnaire (HAQ) Visit 1 (Baseline visit)	0.54 score on a scale Standard Deviation 0.55
Change in Disability Index as Assessed by Health Assessment Questionnaire (HAQ) Visit 4 (Week 24)	-0.07 score on a scale Standard Deviation 0.47

SECONDARY outcome

Timeframe: Baseline, Visit 1 (24 weeks = End of Study)

Population: Safety set: All participants who received at least one dose of study drug.

The HAQ is a validated, patient-oriented outcome assessment instrument. The short version '2 page HAQ' was used. It contains the HAQ Disability Index (HAQ-DI), the HAQ visual analog scale (VAS) for pain and the VAS patient global health scale. The VAS is a tool used to help a person rate the intensity of certain sensations and feelings, such as pain. The visual analog scale for pain is a straight line with one end meaning no pain and the other end meaning the worst pain imaginable. For pain intensity, the scale is most commonly anchored by "no pain" (score of 0) and "pain as bad as it could be" or "worst imaginable pain" (score of 100 [100-mm scale]). A higher score indicates greater pain intensity. Change in pain as assessed by VAS indicates the change from baseline at week 24.

Outcome measures

Measure	Letrozole n=261 Participants Participants received 2.5 milligram (mg) of Letrozole tablets orally once daily (QD) for a period of 24 weeks.
Change in Pain as Assessed by Visual Analog Scale (VAS) Scale of the Health Assessment Questionnaire (HAQ) Visit 1 (Baseline visit)	28.9 score on a scale Standard Deviation 24.22
Change in Pain as Assessed by Visual Analog Scale (VAS) Scale of the Health Assessment Questionnaire (HAQ) Visit 4 (Week 24)	-6.4 score on a scale Standard Deviation 29.30

Adverse Events

Letrozole 2.5 mg

Serious events: 5 serious events

Other events: 163 other events

Deaths: 0 deaths

Serious adverse events

Measure	Letrozole 2.5 mg n=261 participants at risk Participants received 2.5 milligram (mg) of Letrozole tablets orally once daily (QD) for a period of 24 weeks.
Hepatobiliary disorders Cholecystitis chronic	0.38% 1/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Post procedural bile leak	0.38% 1/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.38% 1/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Psychiatric disorders Depression	0.38% 1/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Psychiatric disorders Mania	0.38% 1/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.38% 1/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.

Other adverse events

Measure	Letrozole 2.5 mg n=261 participants at risk Participants received 2.5 milligram (mg) of Letrozole tablets orally once daily (QD) for a period of 24 weeks.
Gastrointestinal disorders Constipation	3.1% 8/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	3.1% 8/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	5.0% 13/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
General disorders Fatigue	12.3% 32/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
General disorders Oedema peripheral	3.8% 10/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Infections and infestations Sinusitis	2.7% 7/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	33.7% 88/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	29.9% 78/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	2.3% 6/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Nervous system disorders Headache	3.1% 8/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Psychiatric disorders Depression	5.0% 13/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	2.3% 6/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Alopecia	2.3% 6/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Vascular disorders Hot flush	14.2% 37/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.
Vascular disorders Hypertension	2.3% 6/261 • Adverse events were collected From Start of the Study up to EOS (Week 24) Safety set: All participants who received at least one dose of study drug.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: Novartis.email@novartis.com

Results disclosure agreements

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