Abemaciclib for Patients With Retinoblastoma-Positive, Triple Negative Metastatic Breast Cancer

• ClinicalTrials.gov Identifier: NCT03130439
• Recruitment Status: Terminated
• First Posted: April 26, 2017
• Results First Posted: September 22, 2022
• Last Update Posted: April 30, 2024
• Sponsor: Dana-Farber Cancer Institute
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): Sara Tolaney, MD, Dana-Farber Cancer Institute

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer
• Intervention: Drug: Abemaciclib
• Enrollment: 27

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Abemaciclib
Arm/Group Description	-Abemaciclib was administered orally, twice daily on days 1 to 28 Abemaciclib: Abemaciclib (LY2835219) has been shown in vitro to be a selective ATP-competitive inhibitor of CDK4 and CDK6 kinase activity that prevents the phosphorylation and subsequent inactivation of the Rb tumor suppressor protein, thereby inducing G1 cell cycle arrest and inhibition of cell proliferation.
Period Title: Overall Study
Started	27
Completed	27
Not Completed	0

Baseline Characteristics

Arm/Group Title		Abemaciclib
Arm/Group Description		-Abemaciclib was administered orally, twice daily on days 1 to 28 Abemaciclib: Abemaciclib (LY2835219) has been shown in vitro to be a selective ATP-competitive inhibitor of CDK4 and CDK6 kinase activity that prevents the phosphorylation and subsequent inactivation of the Rb tumor suppressor protein, thereby inducing G1 cell cycle arrest and inhibition of cell proliferation.
Overall Number of Baseline Participants		27
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	27 participants
		61; (41 to 80)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Age at enrollment	Number Analyzed	27 participants
	Less than 50 years old	5 18.5%
	Over 50 years old	22 81.5%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
	Female	27 100.0%
	Male	0 0.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Race	Number Analyzed	27 participants
	White	24 88.9%
	Black	2 7.4%
	Other	1 3.7%
Number of metastatic sites; Median (Full Range); Unit of measure: Sites
	Number Analyzed	27 participants
		7; (3 to 11)
Number of prior lines of systemic therapy for metastatic disease; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
	0	2 7.4%
	1	4 14.8%
	2	14 51.9%
	3	7 25.9%
(Neo)adjuvant therapy; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
	Yes	22 81.5%
	No	5 18.5%
Number of patients recurred within 12 months of their adjuvant systemic therapy; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
		15 55.6%
Prior chemotherapies in any setting; Measure Type: Number; Unit of measure: Participants	Number Analyzed	27 participants
Anthracycline		18
Taxane		22
Eribulin		4
Prior immune therapy for early stage or metastatic disease; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
		12 44.4%
BRCA1 or BRCA2 Mutation; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
	Present	4 14.8%
	Absent	19 70.4%
	Not reported	4 14.8%
Site of metastasis --Lung; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
		12 44.4%
Site of metastasis --Liver; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
		8 29.6%
Site of metastasis --Bone; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
		15 55.6%
Site of metastasis --Brain; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
		6 22.2%
Site of metastasis --Skin; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
		10 37.0%
Site of metastasis --Lymph node; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	27 participants
		23 85.2%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR; Overall Response Rate(ORR) = (CR + PR)/sample size.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Abemaciclib
Arm/Group Description:	-Abemaciclib was administered orally, twice daily on days 1 to 28 Abemaciclib: Abemaciclib (LY2835219) has been shown in vitro to be a selective ATP-competitive inhibitor of CDK4 and CDK6 kinase activity that prevents the phosphorylation and subsequent inactivation of the Rb tumor suppressor protein, thereby inducing G1 cell cycle arrest and inhibition of cell proliferation.
Overall Number of Participants Analyzed	27
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abemaciclib
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Objective Response Rate
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; 0.000 to 0.247
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Progression Free Survival
Description	Progression-Free Survival (PFS) is defined as the time from randomization (or registration) to the earlier of progression (per Response Evaluation Criteria in Solid Tumors 1.1) or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	Baseline to the earlier of progression (per Response Evaluation Criteria in Solid Tumors 1.1), date of death due to any cause, or date of last disease evaluation. Participants will be followed up up to 16.5 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Abemaciclib
Arm/Group Description:	-Abemaciclib was administered orally, twice daily on days 1 to 28 Abemaciclib: Abemaciclib (LY2835219) has been shown in vitro to be a selective ATP-competitive inhibitor of CDK4 and CDK6 kinase activity that prevents the phosphorylation and subsequent inactivation of the Rb tumor suppressor protein, thereby inducing G1 cell cycle arrest and inhibition of cell proliferation.
Overall Number of Participants Analyzed	27
Median (95% Confidence Interval); Unit of Measure: months
	1.94; (1.84 to 11.47)

3. Secondary Outcome

Title	Overall Survival
Description	Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive.
Time Frame	Baseline to date of death due to any cause, or at date last known alive.Participants will be followed once every 6 months until death.Those removed from protocol therapy for unacceptable adverse event(s) will be followed until resolution or stabilization.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Abemaciclib
Arm/Group Description:	-Abemaciclib was administered orally, twice daily on days 1 to 28 Abemaciclib: Abemaciclib (LY2835219) has been shown in vitro to be a selective ATP-competitive inhibitor of CDK4 and CDK6 kinase activity that prevents the phosphorylation and subsequent inactivation of the Rb tumor suppressor protein, thereby inducing G1 cell cycle arrest and inhibition of cell proliferation.
Overall Number of Participants Analyzed	27
Median (95% Confidence Interval); Unit of Measure: months
	8.44; (4.57 to 15.57)

4. Secondary Outcome

Title	Disease Control Rate
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage (compared to baseline) to qualify for partial or complete response (CR or PR) nor sufficient increase (taking as reference the smallest sum of diameters at baseline or while on study, whichever is smallest) to qualify for progressive disease (PD); Disease control rate is defined as CR + PR + SD ≥ 16weeks
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Abemaciclib
Arm/Group Description:	-Abemaciclib was administered orally, twice daily on days 1 to 28 Abemaciclib: Abemaciclib (LY2835219) has been shown in vitro to be a selective ATP-competitive inhibitor of CDK4 and CDK6 kinase activity that prevents the phosphorylation and subsequent inactivation of the Rb tumor suppressor protein, thereby inducing G1 cell cycle arrest and inhibition of cell proliferation.
Overall Number of Participants Analyzed	27
Measure Type: Count of Participants; Unit of Measure: Participants
	6 22.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abemaciclib
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Disease Control Rate
	Estimated Value	0.222
	Confidence Interval	(2-Sided) 95%; 0.086 to 0.423
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Clinical Benefit Rate
Description	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage (compared to baseline) to qualify for partial or complete response (CR or PR) nor sufficient increase (taking as reference the smallest sum of diameters at baseline or while on study, whichever is smallest) to qualify for progressive disease (PD); Clinical benefit rate is defined as CR+PR+SD ≥ 24weeks
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Abemaciclib
Arm/Group Description:	-Abemaciclib was administered orally, twice daily on days 1 to 28 Abemaciclib: Abemaciclib (LY2835219) has been shown in vitro to be a selective ATP-competitive inhibitor of CDK4 and CDK6 kinase activity that prevents the phosphorylation and subsequent inactivation of the Rb tumor suppressor protein, thereby inducing G1 cell cycle arrest and inhibition of cell proliferation.
Overall Number of Participants Analyzed	27
Measure Type: Count of Participants; Unit of Measure: Participants
	4 14.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abemaciclib
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Clinical Benefit Rate
	Estimated Value	0.148
	Confidence Interval	(2-Sided) 95%; 0.042 to 0.337
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	4.1 years
Adverse Event Reporting Description	Serious Adverse Events were defined as Grade 2/3 unexpected events with treatment attribution of possibly/probably/definitely, Grade 4 unexpected events with treatment attribution of possibly/probably/definitely and all Grade 5 events. All remaining AEs are classified as Other AEs (OAE) including Grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all Grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets.
Arm/Group Title	Abemaciclib
Arm/Group Description	-Abemaciclib was administered orally, twice daily on days 1 to 28 Abemaciclib: Abemaciclib (LY2835219) has been shown in vitro to be a selective ATP-competitive inhibitor of CDK4 and CDK6 kinase activity that prevents the phosphorylation and subsequent inactivation of the Rb tumor suppressor protein, thereby inducing G1 cell cycle arrest and inhibition of cell proliferation.
All-Cause Mortality
	Abemaciclib
	Affected / at Risk (%)
Total	24/27 (88.89%)
Serious Adverse Events
	Abemaciclib
	Affected / at Risk (%)
Total	10/27 (37.04%)
Blood and lymphatic system disorders
Anemia †	2/27 (7.41%)
Cardiac disorders
Pericardial effusion †	2/27 (7.41%)
Chest pain-cardiac †	1/27 (3.70%)
Sinus tachycardia †	1/27 (3.70%)
Gastrointestinal disorders
Abdominal pain †	2/27 (7.41%)
Bloating †	1/27 (3.70%)
Colonic obstruction †	1/27 (3.70%)
Constipation †	1/27 (3.70%)
Diarrhea †	2/27 (7.41%)
Nausea †	3/27 (11.11%)
Vomiting †	3/27 (11.11%)
General disorders
Fatigue †	1/27 (3.70%)
Pain †	1/27 (3.70%)
Infections and infestations
Urinary tract infection †	1/27 (3.70%)
Investigations
Blood bilirubin increased †	1/27 (3.70%)
Neutrophil count decreased †	3/27 (11.11%)
Platelet count decreased †	2/27 (7.41%)
Alanine aminotransferase increased †	1/27 (3.70%)
Aspartate aminotransferase increased †	1/27 (3.70%)
Metabolism and nutrition disorders
Dehydration †	2/27 (7.41%)
Hyponatremia †	3/27 (11.11%)
Anorexia †	1/27 (3.70%)
Hypokalemia †	2/27 (7.41%)
Musculoskeletal and connective tissue disorders
Flank pain †	1/27 (3.70%)
Generalized muscle weakness †	2/27 (7.41%)
Back pain †	1/27 (3.70%)
Nervous system disorders
Presyncope †	1/27 (3.70%)
Dizziness †	1/27 (3.70%)
Psychiatric disorders
Depression †	1/27 (3.70%)
Confusion †	1/27 (3.70%)
Respiratory, thoracic and mediastinal disorders
Cough †	1/27 (3.70%)
Hypoxia †	1/27 (3.70%)
Pneumonitis †	1/27 (3.70%)
Respiratory failure †	1/27 (3.70%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Abemaciclib
	Affected / at Risk (%)
Total	27/27 (100.00%)
Blood and lymphatic system disorders
Anemia †	9/27 (33.33%)
Lymph node pain †	2/27 (7.41%)
Gastrointestinal disorders
Abdominal pain †	7/27 (25.93%)
Bloating †	4/27 (14.81%)
Constipation †	9/27 (33.33%)
Diarrhea †	21/27 (77.78%)
Dyspepsia †	3/27 (11.11%)
Flatulence †	4/27 (14.81%)
Gastroesophageal reflux disease †	3/27 (11.11%)
Mucositis oral †	2/27 (7.41%)
Nausea †	15/27 (55.56%)
Stomach pain †	2/27 (7.41%)
Vomiting †	12/27 (44.44%)
Oral pain †	2/27 (7.41%)
General disorders
Edema limbs †	2/27 (7.41%)
Fatigue †	19/27 (70.37%)
Gait disturbance †	2/27 (7.41%)
Pain †	5/27 (18.52%)
Investigations
Creatinine increased †	5/27 (18.52%)
Neutrophil count decreased †	12/27 (44.44%)
Platelet count decreased †	8/27 (29.63%)
Metabolism and nutrition disorders
Anorexia †	11/27 (40.74%)
Dehydration †	2/27 (7.41%)
Hypokalemia †	2/27 (7.41%)
Hyponatremia †	2/27 (7.41%)
Musculoskeletal and connective tissue disorders
Back pain †	5/27 (18.52%)
Generalized muscle weakness †	3/27 (11.11%)
Neck pain †	3/27 (11.11%)
Bone pain †	3/27 (11.11%)
Nervous system disorders
Dizziness †	2/27 (7.41%)
Dysgeusia †	2/27 (7.41%)
Headache †	6/27 (22.22%)
Presyncope †	2/27 (7.41%)
Peripheral sensory neuropathy †	7/27 (25.93%)
Psychiatric disorders
Anxiety †	5/27 (18.52%)
Depression †	2/27 (7.41%)
Respiratory, thoracic and mediastinal disorders
Cough †	4/27 (14.81%)
Dyspnea †	5/27 (18.52%)
Pneumonitis †	3/27 (11.11%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Sara Tolaney, MD, MPH
• Organization: Dana-Farber Cancer Institute
• Phone: 617-632-5743
• EMail: Sara_Tolaney@dfci.harvard.edu

• Responsible Party: Sara Tolaney, MD, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT03130439
• Other Study ID Numbers: 17-024
• First Submitted: April 24, 2017
• First Posted: April 26, 2017
• Results First Submitted: August 26, 2022
• Results First Posted: September 22, 2022
• Last Update Posted: April 30, 2024