Trial Outcomes & Findings for Neoadjuvant TDM1 With Lapatinib and Abraxane Compared With Trastuzumab Plus Pertuzumab With Paclitaxel (NCT NCT02073487)

NCT ID: NCT02073487

Last Updated: 2021-09-22

Results Overview

To evaluate the pathological complete response (pCR) in the breast after treatment with Trastuzumab Emtansine plus Lapatinib follow by Abraxane in women with HER2 Neu over-expressed breast cancer patients 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.", or similar definition that is accurate and appropriate. Residual cancer burden (RCB)-0 was synonymous with pCR, indicating no residual disease present.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

From date of randomization until the date of surgery, approximately 16 weeks

Results posted on

2021-09-22

Participant Flow

16 patients were enrolled into each arm of the study, for a total of 32 patients. The trial was closed early due to superiority, with 14 patients completing the experimental arm and 16 patients completing the standard, control arm.

Participant milestones

Participant milestones
Measure	T-DM1 + Lapatinib + Abraxane T-DM1 intravenously (IV) every three weeks plus L orally once daily for 6 weeks followed by abraxane IV weekly for 12 weeks. T-DM1: antibody-drug conjugate of trastuzumab and emtansine Lapatinib: Dual tyrosine kinase inhibitor (HER2 and EGFR) Abraxane: albumin-bound paclitaxel. chemotherapy - microtubule inhibitor.	Trastuzumab + Pertuzumab + Paclitaxel Trastuzumab IV weekly plus pertuzumab IV every 3 weeks for 6 weeks, followed by paclitaxel IV weekly for 12 weeks. Trastuzumab: anti-Her2 monoclonal antibody Paclitaxel: chemotherapy - microtubule inhibitor Pertuzumab: anti-HER2 monoclonal antibody
Overall Study STARTED	16	16
Overall Study COMPLETED	14	16
Overall Study NOT COMPLETED	2	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Neoadjuvant TDM1 With Lapatinib and Abraxane Compared With Trastuzumab Plus Pertuzumab With Paclitaxel

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	T-DM1 + Lapatinib + Abraxane n=14 Participants T-DM1 intravenously (IV) every three weeks plus Lapatinib orally once daily for 6 weeks followed by abraxane IV weekly for 12 weeks. T-DM1: antibody-drug conjugate of trastuzumab and emtansine Lapatinib: Dual tyrosine kinase inhibitor (HER2 and EGFR) Abraxane: albumin-bound paclitaxel. chemotherapy - microtubule inhibitor.	Trastuzumab + Pertuzumab + Paclitaxel n=16 Participants Trastuzumab IV weekly plus pertuzumab IV every 3 weeks for 6 weeks, followed by paclitaxel IV weekly for 12 weeks. Trastuzumab: anti-Her2 monoclonal antibody Paclitaxel: chemotherapy - microtubule inhibitor Pertuzumab: anti-HER2 monoclonal antibody	Total n=30 Participants Total of all reporting groups
Age, Continuous	53.1 years n=93 Participants	57.2 years n=4 Participants	55.1 years n=27 Participants
Sex: Female, Male Female	14 Participants n=93 Participants	16 Participants n=4 Participants	30 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=93 Participants	4 Participants n=4 Participants	9 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=93 Participants	12 Participants n=4 Participants	21 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) White	12 Participants n=93 Participants	15 Participants n=4 Participants	27 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	14 participants n=93 Participants	16 participants n=4 Participants	30 participants n=27 Participants
Invasive ductal carcinoma	13 Participants n=93 Participants	14 Participants n=4 Participants	27 Participants n=27 Participants
Tumor grade: 2	7 Participants n=93 Participants	8 Participants n=4 Participants	15 Participants n=27 Participants
Tumor grade: 3	7 Participants n=93 Participants	8 Participants n=4 Participants	15 Participants n=27 Participants
Tumor stage: II	7 Participants n=93 Participants	8 Participants n=4 Participants	15 Participants n=27 Participants
Tumor stage: III	7 Participants n=93 Participants	8 Participants n=4 Participants	15 Participants n=27 Participants

PRIMARY outcome

Timeframe: From date of randomization until the date of surgery, approximately 16 weeks

Outcome measures

Outcome measures
Measure	T-DM1 + Lapatinib + Abraxane n=14 Participants T-DM1 intravenously (IV) every three weeks plus L orally once daily for 6 weeks followed by abraxane IV weekly for 12 weeks. T-DM1: antibody-drug conjugate of trastuzumab and emtansine Lapatinib: Dual tyrosine kinase inhibitor (HER2 and EGFR) Abraxane: albumin-bound paclitaxel. chemotherapy - microtubule inhibitor.	Trastuzumab + Pertuzumab + Paclitaxel n=16 Participants Trastuzumab IV weekly plus pertuzumab IV every 3 weeks for 6 weeks, followed by paclitaxel IV weekly for 12 weeks. Trastuzumab: anti-Her2 monoclonal antibody Paclitaxel: chemotherapy - microtubule inhibitor Pertuzumab: anti-HER2 monoclonal antibody
Pathological Complete Response (pCR) RCB-0 or RCB-1	14 Participants	10 Participants

SECONDARY outcome

Timeframe: From date of randomization until 6 weeks post treatment

Population: Since all patients in the experimental arm achieved RCB-0 or RCB-1 (pCR), changes in tumor size by MRI were only evaluated in patients on the standard arm. Of 16 patients enrolled in the standard arm, 5 had incomplete imaging data. Therefore, 11 patients were analyzed.

To determine the change in tumor size by MRI at 6 weeks post treatment using RECIST v1.0. Criteria. Since all patients in the experimental arm achieved RCB-0 or RCB-1 (pCR), changes in tumor size by MRI were only evaluated in patients on the standard arm.

Outcome measures

Outcome measures
Measure	T-DM1 + Lapatinib + Abraxane n=11 Participants T-DM1 intravenously (IV) every three weeks plus L orally once daily for 6 weeks followed by abraxane IV weekly for 12 weeks. T-DM1: antibody-drug conjugate of trastuzumab and emtansine Lapatinib: Dual tyrosine kinase inhibitor (HER2 and EGFR) Abraxane: albumin-bound paclitaxel. chemotherapy - microtubule inhibitor.	Trastuzumab + Pertuzumab + Paclitaxel Trastuzumab IV weekly plus pertuzumab IV every 3 weeks for 6 weeks, followed by paclitaxel IV weekly for 12 weeks. Trastuzumab: anti-Her2 monoclonal antibody Paclitaxel: chemotherapy - microtubule inhibitor Pertuzumab: anti-HER2 monoclonal antibody
Breast Imaging Response to Treatment: Number of Eventual Responders in Standard Arm	5 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: approximately 1 year

To determine predictive markers for sensitivity and resistance to Trastuzumab Emtansine when combined with Lapatinib follow by Abraxane

Outcome measures

Outcome data not reported

Adverse Events

T-DM1 + Lapatinib + Abraxane

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Trastuzumab + Pertuzumab + Paclitaxel

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Jenny Chang

Houston Methodist

Phone: 713-441-0681

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	T-DM1 + Lapatinib + Abraxane n=14 participants at risk T-DM1 intravenously (IV) every three weeks plus L orally once daily for 6 weeks followed by abraxane IV weekly for 12 weeks. T-DM1: antibody-drug conjugate of trastuzumab and emtansine Lapatinib: Dual tyrosine kinase inhibitor (HER2 and EGFR) Abraxane: albumin-bound paclitaxel. chemotherapy - microtubule inhibitor.	Trastuzumab + Pertuzumab + Paclitaxel n=16 participants at risk Trastuzumab IV weekly plus pertuzumab IV every 3 weeks for 6 weeks, followed by paclitaxel IV weekly for 12 weeks. Trastuzumab: anti-Her2 monoclonal antibody Paclitaxel: chemotherapy - microtubule inhibitor Pertuzumab: anti-HER2 monoclonal antibody
Hepatobiliary disorders Liver Function Abnormality	64.3% 9/14 • From time of informed consent through 30 days after the last treatment dose.	68.8% 11/16 • From time of informed consent through 30 days after the last treatment dose.
General disorders Fatigue	50.0% 7/14 • From time of informed consent through 30 days after the last treatment dose.	50.0% 8/16 • From time of informed consent through 30 days after the last treatment dose.
Gastrointestinal disorders Diarrhea	50.0% 7/14 • From time of informed consent through 30 days after the last treatment dose.	43.8% 7/16 • From time of informed consent through 30 days after the last treatment dose.
Nervous system disorders Neuropathy	21.4% 3/14 • From time of informed consent through 30 days after the last treatment dose.	18.8% 3/16 • From time of informed consent through 30 days after the last treatment dose.
Skin and subcutaneous tissue disorders Rash	21.4% 3/14 • From time of informed consent through 30 days after the last treatment dose.	18.8% 3/16 • From time of informed consent through 30 days after the last treatment dose.
Blood and lymphatic system disorders Hypokalemia	21.4% 3/14 • From time of informed consent through 30 days after the last treatment dose.	37.5% 6/16 • From time of informed consent through 30 days after the last treatment dose.
Blood and lymphatic system disorders Hypomagnesemia	0.00% 0/14 • From time of informed consent through 30 days after the last treatment dose.	6.2% 1/16 • From time of informed consent through 30 days after the last treatment dose.
General disorders Mucositis	7.1% 1/14 • From time of informed consent through 30 days after the last treatment dose.	6.2% 1/16 • From time of informed consent through 30 days after the last treatment dose.
General disorders Nail discoloration	7.1% 1/14 • From time of informed consent through 30 days after the last treatment dose.	0.00% 0/16 • From time of informed consent through 30 days after the last treatment dose.
Skin and subcutaneous tissue disorders Skin Discoloration	7.1% 1/14 • From time of informed consent through 30 days after the last treatment dose.	0.00% 0/16 • From time of informed consent through 30 days after the last treatment dose.
General disorders Nausea	0.00% 0/14 • From time of informed consent through 30 days after the last treatment dose.	18.8% 3/16 • From time of informed consent through 30 days after the last treatment dose.
Gastrointestinal disorders Constipation	7.1% 1/14 • From time of informed consent through 30 days after the last treatment dose.	0.00% 0/16 • From time of informed consent through 30 days after the last treatment dose.
Psychiatric disorders Depression	7.1% 1/14 • From time of informed consent through 30 days after the last treatment dose.	6.2% 1/16 • From time of informed consent through 30 days after the last treatment dose.
Psychiatric disorders Anxiety	0.00% 0/14 • From time of informed consent through 30 days after the last treatment dose.	6.2% 1/16 • From time of informed consent through 30 days after the last treatment dose.
General disorders Epistaxis	14.3% 2/14 • From time of informed consent through 30 days after the last treatment dose.	0.00% 0/16 • From time of informed consent through 30 days after the last treatment dose.
General disorders Chest pain	0.00% 0/14 • From time of informed consent through 30 days after the last treatment dose.	6.2% 1/16 • From time of informed consent through 30 days after the last treatment dose.
Cardiac disorders Myocardial infarction	7.1% 1/14 • From time of informed consent through 30 days after the last treatment dose.	0.00% 0/16 • From time of informed consent through 30 days after the last treatment dose.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/14 • From time of informed consent through 30 days after the last treatment dose.	6.2% 1/16 • From time of informed consent through 30 days after the last treatment dose.
General disorders Breast pain	0.00% 0/14 • From time of informed consent through 30 days after the last treatment dose.	6.2% 1/16 • From time of informed consent through 30 days after the last treatment dose.
Blood and lymphatic system disorders Platelet count decreased	7.1% 1/14 • From time of informed consent through 30 days after the last treatment dose.	0.00% 0/16 • From time of informed consent through 30 days after the last treatment dose.
Blood and lymphatic system disorders Neutrophil count decreased	7.1% 1/14 • From time of informed consent through 30 days after the last treatment dose.	0.00% 0/16 • From time of informed consent through 30 days after the last treatment dose.