DS-8201a Versus T-DM1 for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [DESTINY-Breast03]

• Sponsor: Daiichi Sankyo, Inc. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03529110
• Collaborator: Daiichi Sankyo Co., Ltd. (Industry), AstraZeneca (Industry)
• Enrollment: 524
• Locations: 164
• Arms: 2
• Anticipated Duration (Months): 55.7
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is designed to compare the anti-tumor activity as well as the safety and efficacy of DS-8201a versus T-DM1 in HER2-positive, unresectable and/or metastatic breast cancer subjects previously treated with trastuzumab and taxane.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Trastuzumab deruxtecan (T-DXd); Drug: Ado-trastuzumab emtansine (T-DM1)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 524 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Study of DS-8201a (Trastuzumab Deruxtecan), an Anti-HER2 Antibody Drug Conjugate (ADC), Versus Ado Trastuzumab Emtansine (T-DM1) for HER2-Positive, Unresectable and/or Metastatic Breast Cancer Subjects Previously Treated With Trastuzumab and Taxane
• Actual Study Start Date: Aug 9, 2018
• Actual Primary Completion Date: May 21, 2021
• Anticipated Study Completion Date: Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Trastuzumab deruxtecan (T-DXd) Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).	Drug: Trastuzumab deruxtecan (T-DXd); T-DXd is sterile lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered intravenously.; Other Names: DS-8201a
Active Comparator: Ado-trastuzumab emtansine (T-DM1) Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.	Drug: Ado-trastuzumab emtansine (T-DM1); The treatment will be in accordance with the approved label.; Other Names: T-DM1

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [Up to 33 months (data cut-off)]

   Progression-free survival (PFS) by BICR was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.

Secondary Outcome Measures

1. Overall Survival (OS) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [Up to 33 months (data cut-off)]

   Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause.

2. Percentage of Participants With Objective Response Rate (ORR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [Up to 33 months (data cut-off)]

   The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by BICR and investigator assessment based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR is reported.

3. Duration of Response (DoR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [Up to 33 months (data cut-off)]

   Duration of Response (DoR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR in participants with confirmed CR/PR based on BICR and investigator assessment is reported.

4. Progression-Free Survival (PFS) Based on Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [Up to 33 months (data cut-off)]

   Progression-free survival (PFS) by investigator assessment was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Is the age of majority in their country

• Has pathologically documented breast cancer that:

1. is unresectable or metastatic

2. has confirmed HER2-positive expression as determined according to American Society of Clinical Oncology - College of American Pathologists guidelines evaluated at a central laboratory

3. was previously treated with trastuzumab and taxane in the advanced/metastatic setting or progressed within 6 months after neoadjuvant or adjuvant treatment involving a regimen including trastuzumab and taxane

• Has documented radiologic progression (during or after most recent treatment or within 6 months after completing adjuvant therapy)

• Is HER2 positive as confirmed by central laboratory assessment of most recent tumor tissue sample available. If archived tissue is not available, agrees to provide a fresh biopsy.

• If of reproductive/childbearing potential, agrees to use a highly effective form of contraception or avoid intercourse during and upon completion of the study for 7 months after the last dose of DS-8201a (females); 4.5 months after last dose of DS-8201a (males) or 7 months after the last dose of T-DM1

• Has adequate renal and hepatic function

Exclusion Criteria:

• Has previously been treated with an anti-HER2 antibody drug conjugate (ADC) in the metastatic setting. Prior treatment in the adjuvant/neo-adjuvant setting would be allowed if progression of disease did not occur within 12 months of end of adjuvant therapy

• Has uncontrolled or significant cardiovascular disease

• Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening

• Has spinal cord compression or clinically active central nervous system (CNS) metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.

1. Participants with clinically inactive brain metastases may be included in the study.

2. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Hematology Oncology	Los Angeles	California	United States	90095
2	Sharp Memorial Hospital	San Diego	California	United States	92123
3	University of California San Francisco	San Francisco	California	United States	94115
4	Innovative Clinical Research Institute	Whittier	California	United States	90603
5	Washington Cancer Institute	Washington	District of Columbia	United States	20010
6	Florida Cancer Specialists-Broadway	Fort Myers	Florida	United States	33916
7	Florida Cancer Specialists NORTH	Saint Petersburg	Florida	United States	33705
8	Piedmont Cancer Institute, PC	Atlanta	Georgia	United States	30318
9	Loyola University Health System	Maywood	Illinois	United States	60153
10	Norton Cancer Institute	Louisville	Kentucky	United States	40207
11	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
12	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
13	North Shore Hematology Oncology Associates, PC	East Setauket	New York	United States	11733
14	University of Rochester	Rochester	New York	United States	14642
15	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
16	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45267
17	Seidman Cancer Center	Cleveland	Ohio	United States	44106
18	The Ohio State University	Columbus	Ohio	United States	43210
19	Dayton Physicians, LLC	Kettering	Ohio	United States	45409
20	Magee-Womens Hospital of UPMC	Pittsburgh	Pennsylvania	United States	15213
21	Tennessee Oncology- St Thomas Location	Nashville	Tennessee	United States	37205
22	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee	United States	37232
23	UT Southwestern Medical Center	Dallas	Texas	United States	75390-8857
24	Houston Methodist Hospital / Houston Methodist Cancer Center	Houston	Texas	United States	77030
25	MD Anderson Cancer Center	Houston	Texas	United States	77030
26	Millennium Oncology	Houston	Texas	United States	77090
27	The University of Texas Health Science Center at Tyler	Tyler	Texas	United States	75708
28	MultiCare Health System Institute for Research and Innovation	Auburn	Washington	United States	98001
29	The Tweed Hospital	Tweed Heads	New South Wales	Australia	2485
30	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
31	Box Hill Hospital	Box Hill	Victoria	Australia	3128
32	Peninsula and South Eastern Haematology & Oncology Group	Frankston	Victoria	Australia	3199
33	Peter MacCallum Cancer	Melbourne	Victoria	Australia	3000
34	St John of God Subiaco Hospital	Subiaco	Western Australia	Australia	6008
35	Institut Jules-Bordet	Bruxelles		Belgium	1000
36	Universitair Ziekenhuis Brussel	Bruxelles		Belgium	1090
37	Universitair Ziekenhuis Antwerpen	Edegem		Belgium	2650
38	AZ Sint-Lucas - Campus Sint-Lucas	Gent		Belgium	9000
39	Universitaire Ziekenhuizen Leuven	Leuven		Belgium	3000
40	CHU UCL Namur site de Sainte Elisabeth	Namur		Belgium	5000
41	NOB - Nucleo de Oncologia da Bahia	Salvador	Bahia	Brazil	40170-110
42	Hospital Nossa Senhora da Conceição	Porto Alegre	Rio Grande Do Sul	Brazil	91350-200
43	Clínica de Neoplasias Litoral Ltda.	Itajaí	Santa Catarina	Brazil	88301-220
44	CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia	Santo André	Sao Paulo	Brazil	09060-650
45	ICESP - Instituto do Cancer do Estado de São Paulo Octavio Frias de Oliveira	São Paulo	Sao Paulo	Brazil	01246-000
46	Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda.	São Paulo	Sao Paulo	Brazil	01317-001
47	COI - Clínicas Oncológicas Integradas	Rio De Janeiro		Brazil	22793-080
48	A. C. Camargo Cancer Center	São Paulo		Brazil	01509-900
49	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N 4N2
50	Toronto Sunnybrook Hospital	Toronto	Ontario	Canada	M4N 3M5
51	St. Mary's Hospital	Montréal	Quebec	Canada	H3T 1M5
52	Cancer Hospital Chinese Academy of Medical Sciences	Beijing	Beijing	China	100021
53	Beijing Hospital	Beijing	Beijing	China	100730
54	Sun Yat-sen University, Cancer Center	Guangzhou	Guangdong	China	510060
55	Sun Yat-sen Memorial Hospital, Sun Yat-sen University	Guangzhou	Guangdong	China	510120
56	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang	China	150081
57	The First Hospital of Jilin University	Chang chun	Jilin	China	130021
58	Liaoning Cancer Hospital & Institute	Shenyang	Liaoning	China	110042
59	Fudan University Shanghai Cancer Center	Shanghai	Shanghai	China	200032
60	West China Hospital, Sichuan University	Chengdu	Sichuan	China	610041
61	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin	China	300060
62	Sir Run Run Shaw Hospital Xiasha Branch, Zhejiang University, School of Medicine	Hangzhou	Zhejiang	China	310000
63	Zhejiang Cancer Hospital	Hangzhou	Zhejiang	China	310022
64	Centre Paul Strauss	Strasbourg Cedex	Bas Rhin	France	67000
65	Hôpital Nord - CHU Marseille	Marseille Cedex 20	Bouches-du-Rhone	France	13915
66	Centre François Baclesse	Caen Cedex 05	Calvados	France	14076
67	Clinique Victor Hugo - Centre Jean Bernard	Le Mans	Cedex 02, Sarthe	France	72015
68	CARIO - Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie	Plérin	Cotes d'Armor	France	22190
69	Centre Georges François Leclerc	Dijon cedex	Côte-d'Or	France	21079
70	CHRU Jean Minjoz	Besançon	Doubs	France	25030
71	Institut Bergonié	Bordeaux cedex	Gironde	France	33076
72	Centre René Huguenin	Saint-Cloud	Hauts De Seine	France	92110
73	ICM Val d'Aurelle	Montpellier	Herault	France	34298
74	CRLCC Eugene Marquis	Rennes cedex	Ille Et Vilaine	France	35042
75	Institut de cancérologie de l'ouest, site René Gauducheau	Saint-Herblain	Loire Atlantique	France	44805
76	ICO - Site Paul Papin	Angers Cedex 2	Maine Et Loire	France	49055
77	Centre de cancerologie les Dentellieres	Valenciennes	Nord	France	59300
78	Centre Leon Berard	Lyon Cedex 08	Rhone	France	69373
79	Centre Hospitalier Lyon Sud	Pierre Benite Cedex	Rhone	France	69495
80	Institut Sainte Catherine	Avignon Cedex 9	Vaculuse	France	84918
81	Hôpital d'Instruction des Armees Begin*	Saint-Mandé	Val De Marne	France	94160
82	Institut Gustave Roussy	Villejuif cedex	Val De Marne	France	94805
83	Institut Curie - site de Paris	Paris		France	75005
84	Hôpital Saint-Louis	Paris		France	75010
85	Hopital Tenon	Paris		France	75020
86	Universitaetsklinikum Erlangen	Erlangen	Bayern	Germany	91-54
87	Rotkreuzklinikum Muenchen gGmbH	Muenchen	Bayern	Germany	80637
88	Klinikum rechts der Isar der TU Muenchen	Muenchen	Bayern	Germany	81675
89	Universitaetsklinikum Duesseldorf AoeR	Düsseldorf	Nordrhein Westfalen	Germany	40225
90	Haematologisch-Onkologische Schwerpunktpraxis	Troisdorf	Nordrhein Westfalen	Germany	53840
91	Marienhospital Bottrop gGmbH	Bottrop	Rheinland Pfalz	Germany	46236
92	Universitaetsklinikum Schleswig-Holstein - Campus Luebeck	Luebeck	Schleswig Holstein	Germany	23538
93	Queen Mary Hospital	Hong Kong		Hong Kong	00000
94	Chinese University of Hong Kong	Shatin		Hong Kong	00000
95	Azienda Ospedaliera Universitaria Arcispedale Sant'Anna	Cona	Ferrara	Italy	44124
96	Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo), U.O Oncologia Medica	Monza	Milano	Italy	20900
97	Istituto Clinico Humanitas	Rozzano	Milano	Italy	20089
98	IRCCS Centro di Riferimento Oncologico	Aviano	Pordenone	Italy	33081
99	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)	Bergamo		Italy	24127
100	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi	Bologna		Italy	40138
101	Istituto Nazionale per la Ricerca sul Cancro di Genova	Genova		Italy	16132
102	Azienda Ospealiera della Provincia di Lecco	Lecco		Italy	23900
103	Azienda Ospedaliera Ospedali Riuniti Papardo-Piemonte	Messina		Italy	98158
104	Ospedale San Raffaele	Milano		Italy	20132
105	IEO Istituto Europeo di Oncologia	Milano		Italy	20141
106	A.O.U. Policlinico di Modena	Modena		Italy	41124
107	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli		Italy	80131
108	Azienda Ospedaliero Universitaria di Parma	Parma		Italy	43100
109	Fondazione IRCCS Policlinico San Matteo	Pavia		Italy	27100
110	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino		Italy	10126
111	Center Hospital of the National Center for Global Health and Medicine	Shinjuku-Ku	Tokyo-To	Japan	162-8655
112	Aichi Cancer Center Hospital	Aichi		Japan	464-8681
113	NHO Shikoku Cancer Center	Ehime		Japan	791-0280
114	NHO Kyushu Cancer Center	Fukuoka		Japan	811-1395
115	Hiroshima City Hiroshima Citizens Hospital	Hiroshima		Japan	730-8518
116	NHO Hokkaido Cancer Center	Hokkaido		Japan	003-0804
117	Kanagawa Cancer Center	Kanagawa		Japan	241-8515
118	Kumamoto University Hospital	Kumamoto		Japan	860-8556
119	Niigata Cancer Center	Niigata		Japan	951-8566
120	Okayama University Hospital	Okayama		Japan	700-8558
121	NHO Osaka National Hospital	Osaka		Japan	540-0006
122	Osaka International Cancer Institute	Osaka		Japan	541-8567
123	Saitama Cancer Center	Saitama		Japan	362-0806
124	Shizuoka Cancer Center	Shizuoka		Japan	411-8777
125	National Cancer Center Hospital	Tokyo		Japan	104-0045
126	The Cancer Institute Hospital of JFCR	Tokyo		Japan	135-8550
127	Showa University Hospital	Tokyo		Japan	142-8666
128	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
129	Seoul National University Hospital	Seoul		Korea, Republic of	03080
130	Severance Hospital, Yonsei University	Seoul		Korea, Republic of	03722
131	Asan Medical Center	Seoul		Korea, Republic of	05505
132	Samsung Medical Center	Seoul		Korea, Republic of	06351
133	ICO l'Hospitalet - Hospital Duran i Reynals	L'Hospitalet De Llobregat	Barcelona	Spain	08908
134	Complejo Hospitalario Universitario A Coruña	A Coruña	La Coruña	Spain	15006
135	Complejo Hospitalario Universitario de Santiago	Santiago De Compostela	La Coruña	Spain	15706
136	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid	Spain	28222
137	Hospital Universitario Virgen Macarena	Sevilla	Sevill	Spain	41009
138	Hospital Universitario de Canarias	San Cristobal de la Laguna	Tenerife	Spain	38320
139	Hospital Infanta Cristina	Badajoz		Spain	6007
140	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
141	Hospital Clinic de Barcelona	Barcelona		Spain	08036
142	IOB-Institute of Oncology	Barcelona		Spain	8023
143	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007
144	MD Anderson Cancer Centre	Madrid		Spain	28033
145	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
146	Hospital Universitario Clinico San Carlos	Madrid		Spain	28040
147	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
148	Hospital Clinico Universitario Virgen de la Victoria	Málaga		Spain	29010
149	Hospital Universitario Virgen del Rocio	Sevilla		Spain	41013
150	China Medical University Hospital	Taichung		Taiwan	40447
151	National Cheng Kung University Hospital	Tainan		Taiwan	704
152	National Taiwan University Hospital	Taipei		Taiwan	100
153	Taipei Veterans General Hospital	Taipei		Taiwan	11217
154	Koo Foundation, Sun Yat-Sen Cancer Center	Taipei		Taiwan	112
155	Royal Devon and Exeter Hospital (Wonford)	Exeter	Devon	United Kingdom	EX2 5DW
156	Aberdeen Royal Infirmary	Aberdeen	Grampian Region	United Kingdom	AB25 2ZB
157	Queen Mary University of London	London	Greater London	United Kingdom	EC1M 6BQ
158	University College London Hospitals	London	Greater London	United Kingdom	NW1 2PG
159	Guy's Hospital	London	Greater London	United Kingdom	SE1 9RY
160	Sarah Cannon Research Institute UK	London	Greater London	United Kingdom	W1G 6AD
161	The Christie NHS Foundation Trust	Manchester	Greater Manchester	United Kingdom	M20 4BX
162	Western General Hospital	Edinburgh	Lothian Region	United Kingdom	EH4 2XU
163	Nottingham University Hospitals City Campus	Nottingham	Nottinghamshire	United Kingdom	NG5 1PB
164	Royal Surrey County Hospital	Guildford	Surrey	United Kingdom	GU2 7XX

Sponsors and Collaborators

• Daiichi Sankyo, Inc.
• Daiichi Sankyo Co., Ltd.
• AstraZeneca

Investigators

• Study Director: Global Team Leader, Daiichi Sankyo, Inc.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 25, 2020

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo, Inc.
• ClinicalTrials.gov Identifier: NCT03529110
• Other Study ID Numbers: DS8201-A-U302; 2018-000222-61; 183976; DESTINY-B03
• First Posted: May 18, 2018
• Last Update Posted: Apr 29, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Daiichi Sankyo, Inc.: Breast Cancer; Metastatic breast cancer; DS-8201a; DESTINY - Breast 03
• Additional relevant MeSH terms: Breast Neoplasms; Trastuzumab; Ado-Trastuzumab Emtansine; Maytansine

Study Results

Participant Flow

Recruitment Details	A total of 524 participants were enrolled and treated at study sites in 14 countries. Primary results reported is from first participant randomized up to data cut-off date of 21 May 2021. The results presented are based on primary analysis up to 33 months. Data collection is still on-going and additional results will be provided after study completion.

Arm/Group Title	Trastuzumab Deruxtecan (T-DXd)	Ado-trastuzumab Emtansine (T-DM1)
Arm/Group Description	Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).	Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.
Period Title: Overall Study
STARTED	261	263
COMPLETED	136	49
NOT COMPLETED	125	214

Baseline Characteristics

Arm/Group Title	Trastuzumab Deruxtecan (T-DXd)	Ado-trastuzumab Emtansine (T-DM1)	Total
Arm/Group Description	Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).	Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.	Total of all reporting groups
Overall Participants	261	263	524
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	212 81.2%	206 78.3%	418 79.8%
>=65 years	49 18.8%	57 21.7%	106 20.2%
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	54.5 (11.11)	54.2 (11.84)	54.4 (11.47)
Sex: Female, Male (Count of Participants)
Female	260 99.6%	262 99.6%	522 99.6%
Male	1 0.4%	1 0.4%	2 0.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	152 58.2%	162 61.6%	314 59.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	10 3.8%	9 3.4%	19 3.6%
White	71 27.2%	72 27.4%	143 27.3%
More than one race	2 0.8%	0 0%	2 0.4%
Unknown or Not Reported	26 10%	20 7.6%	46 8.8%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
Description	Progression-free survival (PFS) by BICR was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
Time Frame	Up to 33 months (data cut-off)

Outcome Measure Data

Analysis Population Description

Progression-free survival (PFS) was assessed in the Full Analysis Set at data cut-off date of 21 May 2021.

Arm/Group Title	Trastuzumab Deruxtecan (T-DXd)	Ado-trastuzumab Emtansine (T-DM1)
Arm/Group Description	Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).	Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.
Measure Participants	261	263
Median (95% Confidence Interval) [months]	NA	6.8

2. Secondary Outcome

Title	Overall Survival (OS) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
Description	Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause.
Time Frame	Up to 33 months (data cut-off)

Outcome Measure Data

Analysis Population Description

Overall survival (OS) was assessed in the Full Analysis Set at data cut-off date of 21 May 2021.

Arm/Group Title	Trastuzumab Deruxtecan (T-DXd)	Ado-trastuzumab Emtansine (T-DM1)
Arm/Group Description	Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).	Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.
Measure Participants	261	263
Median (95% Confidence Interval) [months]	NA	NA

3. Secondary Outcome

Title	Percentage of Participants With Objective Response Rate (ORR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
Description	The Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by BICR and investigator assessment based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR is reported.
Time Frame	Up to 33 months (data cut-off)

Outcome Measure Data

Analysis Population Description

Objective response rate was assessed in the Full Analysis Set at data cut-off date of 21 May 2021.

Arm/Group Title	Trastuzumab Deruxtecan (T-DXd)	Ado-trastuzumab Emtansine (T-DM1)
Arm/Group Description	Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).	Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.
Measure Participants	261	263
BICR	79.7 30.5%	34.2 13%
Investigator Assessment	77.0 29.5%	36.9 14%

4. Secondary Outcome

Title	Duration of Response (DoR) Based on BICR and Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
Description	Duration of Response (DoR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DoR in participants with confirmed CR/PR based on BICR and investigator assessment is reported.
Time Frame	Up to 33 months (data cut-off)

Outcome Measure Data

Analysis Population Description

Duration of Response (DoR) was assessed in the Full Analysis Set of participants with confirmed CR/PR at data cut-off date of 21 May 2021.

Arm/Group Title	Trastuzumab Deruxtecan (T-DXd)	Ado-trastuzumab Emtansine (T-DM1)
Arm/Group Description	Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).	Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.
Measure Participants	261	263
BICR	NA	NA
Investigator Assessment	NA	NA

5. Secondary Outcome

Title	Progression-Free Survival (PFS) Based on Investigator Assessment in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane
Description	Progression-free survival (PFS) by investigator assessment was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
Time Frame	Up to 33 months (data cut-off)

Outcome Measure Data

Analysis Population Description

Progression-free survival (PFS) was assessed in the Full Analysis Set at data cut-off date of 21 May 2021.

Arm/Group Title	Trastuzumab Deruxtecan (T-DXd)	Ado-trastuzumab Emtansine (T-DM1)
Arm/Group Description	Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).	Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.
Measure Participants	261	263
Median (95% Confidence Interval) [months]	25.1	7.2

Adverse Events

Time Frame	Adverse events (AE) were collected from the date of signing the informed consent form up to 47 days after last dose of the study drug, up 33 months.
Adverse Event Reporting Description	A Treatment-emergent adverse event (TEAE) is defined as an AE that occurs, having been absent before the first dose of study drug, or has worsened in severity or seriousness after the initiating the study drug until 47 days after last dose of the study drug.
Arm/Group Title	Trastuzumab Deruxtecan (T-DXd)		Ado-trastuzumab Emtansine (T-DM1)
Arm/Group Description	Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DXd as a sterile intravenous (IV) solution at a dose of 5.4 mg/kg every 3 weeks (Q3W).		Participants with HER2-positive, unresectable and/or metastatic breast cancer participants previously treated with trastuzumab and taxane who received T-DM1 in accordance with the approved label.
All Cause Mortality
	Trastuzumab Deruxtecan (T-DXd)		Ado-trastuzumab Emtansine (T-DM1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/257 (12.8%)		53/261 (20.3%)
Serious Adverse Events
	Trastuzumab Deruxtecan (T-DXd)		Ado-trastuzumab Emtansine (T-DM1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/257 (19.1%)		47/261 (18%)
Blood and lymphatic system disorders
Anaemia	2/257 (0.8%)		3/261 (1.1%)
Febrile neutropenia	2/257 (0.8%)		0/261 (0%)
Ear and labyrinth disorders
Otolithiasis	0/257 (0%)		1/261 (0.4%)
Endocrine disorders
Hypercalcaemia of malignancy	0/257 (0%)		1/261 (0.4%)
Eye disorders
Rhegmatogenous retinal detachment	1/257 (0.4%)		0/261 (0%)
Gastrointestinal disorders
Vomiting	5/257 (1.9%)		2/261 (0.8%)
Nausea	2/257 (0.8%)		0/261 (0%)
Abdominal pain	1/257 (0.4%)		1/261 (0.4%)
Constipation	1/257 (0.4%)		1/261 (0.4%)
Campylobacter gastroenteritis	1/257 (0.4%)		0/261 (0%)
Colitis	1/257 (0.4%)		0/261 (0%)
Gastrointestinal disorder	1/257 (0.4%)		0/261 (0%)
Gastrointestinal polyp haemorrhage	1/257 (0.4%)		0/261 (0%)
Haematemesis	1/257 (0.4%)		0/261 (0%)
Diarrhoea	0/257 (0%)		1/261 (0.4%)
General disorders
Pyrexia	4/257 (1.6%)		0/261 (0%)
Disease progression	3/257 (1.2%)		1/261 (0.4%)
General physical health deterioration	1/257 (0.4%)		0/261 (0%)
Oedema peripheral	1/257 (0.4%)		0/261 (0%)
Sudden death	1/257 (0.4%)		0/261 (0%)
Fatigue	0/257 (0%)		1/261 (0.4%)
Hepatobiliary disorders
Jaundice cholestatic	1/257 (0.4%)		0/261 (0%)
Hepatic atrophy	0/257 (0%)		1/261 (0.4%)
Hepatic failure	0/257 (0%)		1/261 (0.4%)
Infections and infestations
Pneumonia	4/257 (1.6%)		5/261 (1.9%)
Urinary tract infection	3/257 (1.2%)		1/261 (0.4%)
Cellulitis	2/257 (0.8%)		0/261 (0%)
COVID-19	1/257 (0.4%)		2/261 (0.8%)
Breast cellulitis	1/257 (0.4%)		0/261 (0%)
Cytomegalovirus infection	1/257 (0.4%)		0/261 (0%)
Enterocolitis infectious	1/257 (0.4%)		0/261 (0%)
Infection	1/257 (0.4%)		0/261 (0%)
Influenza	1/257 (0.4%)		0/261 (0%)
Pneumonitis	1/257 (0.4%)		0/261 (0%)
Tracheobronchitis	1/257 (0.4%)		0/261 (0%)
Erysipelas	0/257 (0%)		1/261 (0.4%)
Gastroenteritis	0/257 (0%)		1/261 (0.4%)
Postoperative wound infection	0/257 (0%)		1/261 (0.4%)
Soft tissue infection	0/257 (0%)		1/261 (0.4%)
Injury, poisoning and procedural complications
Femur fracture	1/257 (0.4%)		0/261 (0%)
Radiation necrosis	1/257 (0.4%)		0/261 (0%)
Spinal fracture	1/257 (0.4%)		0/261 (0%)
Thermal burn	1/257 (0.4%)		0/261 (0%)
Brain herniation	0/257 (0%)		1/261 (0.4%)
Femoral neck fracture	0/257 (0%)		1/261 (0.4%)
Lower limb fracture	0/257 (0%)		1/261 (0.4%)
Subdural haematoma	0/257 (0%)		1/261 (0.4%)
Subdural haemorrhage	0/257 (0%)		1/261 (0.4%)
Investigations
Ejection fraction decreased	1/257 (0.4%)		0/261 (0%)
Gamma-glutamyltransferase increased	1/257 (0.4%)		0/261 (0%)
Platelet count decreased	0/257 (0%)		3/261 (1.1%)
Alanine aminotransferase increased	0/257 (0%)		1/261 (0.4%)
Aspartate aminotransferase increased	0/257 (0%)		1/261 (0.4%)
Biopsy lymph gland	0/257 (0%)		1/261 (0.4%)
Blood bilirubin increased	0/257 (0%)		1/261 (0.4%)
Metabolism and nutrition disorders
Hypokalaemia	2/257 (0.8%)		0/261 (0%)
Decreased appetite	1/257 (0.4%)		0/261 (0%)
Dehydration	1/257 (0.4%)		0/261 (0%)
Hyperglycaemia	1/257 (0.4%)		0/261 (0%)
Lactic acidosis	1/257 (0.4%)		0/261 (0%)
Hypercalcaemia	0/257 (0%)		2/261 (0.8%)
Hyponatraemia	0/257 (0%)		1/261 (0.4%)
Musculoskeletal and connective tissue disorders
Back pain	1/257 (0.4%)		0/261 (0%)
Bone lesion	1/257 (0.4%)		0/261 (0%)
Pain in extremity	1/257 (0.4%)		0/261 (0%)
Osteonecrosis of jaw	0/257 (0%)		1/261 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	0/257 (0%)		1/261 (0.4%)
Colon cancer	0/257 (0%)		1/261 (0.4%)
Nervous system disorders
Epilepsy	1/257 (0.4%)		0/261 (0%)
Vasogenic cerebral oedema	1/257 (0.4%)		0/261 (0%)
Altered state of consciousness	0/257 (0%)		1/261 (0.4%)
Optic neuritis	0/257 (0%)		1/261 (0.4%)
Spinal cord compression	0/257 (0%)		1/261 (0.4%)
Pregnancy, puerperium and perinatal conditions
Seizure	2/257 (0.8%)		0/261 (0%)
Renal and urinary disorders
Renal impairment	1/257 (0.4%)		0/261 (0%)
Acute kidney injury	0/257 (0%)		1/261 (0.4%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	5/257 (1.9%)		0/261 (0%)
Acute respiratory failure	1/257 (0.4%)		0/261 (0%)
Dyspnoea	1/257 (0.4%)		0/261 (0%)
Epistaxis	0/257 (0%)		1/261 (0.4%)
Mediastinal cyst	0/257 (0%)		1/261 (0.4%)
Pleural effusion	0/257 (0%)		1/261 (0.4%)
Pneumonia aspiration	0/257 (0%)		1/261 (0.4%)
Pulmonary embolism	0/257 (0%)		1/261 (0.4%)
Vascular disorders
Hypertension	1/257 (0.4%)		0/261 (0%)
Hypotension	1/257 (0.4%)		0/261 (0%)
Angiodysplasia	0/257 (0%)		1/261 (0.4%)
Arterial haemorrhage	0/257 (0%)		1/261 (0.4%)
Haematoma	0/257 (0%)		1/261 (0.4%)
Other (Not Including Serious) Adverse Events
	Trastuzumab Deruxtecan (T-DXd)		Ado-trastuzumab Emtansine (T-DM1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	256/257 (99.6%)		249/261 (95.4%)
Blood and lymphatic system disorders
Anaemia	83/257 (32.3%)		43/261 (16.5%)
Neutropenia	41/257 (16%)		7/261 (2.7%)
Leukopenia	22/257 (8.6%)		8/261 (3.1%)
Lymphopenia	15/257 (5.8%)		6/261 (2.3%)
Thrombocytopenia	13/257 (5.1%)		31/261 (11.9%)
Gastrointestinal disorders
Nausea	195/257 (75.9%)		79/261 (30.3%)
Vomiting	126/257 (49%)		26/261 (10%)
Constipation	88/257 (34.2%)		51/261 (19.5%)
Diarrhoea	75/257 (29.2%)		18/261 (6.9%)
Dyspepsia	29/257 (11.3%)		16/261 (6.1%)
Abdominal pain	29/257 (11.3%)		5/261 (1.9%)
Abdominal pain upper	28/257 (10.9%)		12/261 (4.6%)
Gastrooesophageal reflux disease	13/257 (5.1%)		4/261 (1.5%)
General disorders
Fatigue	74/257 (28.8%)		52/261 (19.9%)
Asthenia	32/257 (12.5%)		31/261 (11.9%)
Malaise	29/257 (11.3%)		10/261 (3.8%)
Pyrexia	27/257 (10.5%)		39/261 (14.9%)
Oedema peripheral	17/257 (6.6%)		9/261 (3.4%)
Infections and infestations
Stomatitis	40/257 (15.6%)		10/261 (3.8%)
Urinary tract infection	19/257 (7.4%)		13/261 (5%)
Pneumonia	18/257 (7%)		9/261 (3.4%)
Pneumonitis	18/257 (7%)		1/261 (0.4%)
Investigations
Neutrophil count decreased	75/257 (29.2%)		25/261 (9.6%)
Aspartate aminotransferase increased	66/257 (25.7%)		105/261 (40.2%)
White blood cell count decreased	58/257 (22.6%)		14/261 (5.4%)
Alanine aminotransferase increased	56/257 (21.8%)		77/261 (29.5%)
Platelet count decreased	54/257 (21%)		112/261 (42.9%)
Blood alkaline phosphatase increased	35/257 (13.6%)		30/261 (11.5%)
Blood lactate dehydrogenase increased	17/257 (6.6%)		35/261 (13.4%)
Blood bilirubin increased	17/257 (6.6%)		13/261 (5%)
Lymphocyte count decreased	14/257 (5.4%)		3/261 (1.1%)
Metabolism and nutrition disorders
Decreased appetite	75/257 (29.2%)		44/261 (16.9%)
Weight decreased	43/257 (16.7%)		16/261 (6.1%)
Hypokalaemia	33/257 (12.8%)		26/261 (10%)
Hypoalbuminaemia	20/257 (7.8%)		12/261 (4.6%)
Musculoskeletal and connective tissue disorders
Back Pain	24/257 (9.3%)		16/261 (6.1%)
Myalgia	23/257 (8.9%)		16/261 (6.1%)
Arthralgia	22/257 (8.6%)		23/261 (8.8%)
Pain in extremity	21/257 (8.2%)		16/261 (6.1%)
Musculoskeletal pain	17/257 (6.6%)		12/261 (4.6%)
Nervous system disorders
Headache	54/257 (21%)		38/261 (14.6%)
Dizziness	32/257 (12.5%)		22/261 (8.4%)
Peripheral sensory neuropathy	19/257 (7.4%)		25/261 (9.6%)
Dysgeusia	15/257 (5.8%)		8/261 (3.1%)
Psychiatric disorders
Anxiety	18/257 (7%)		6/261 (2.3%)
Insomnia	15/257 (5.8%)		24/261 (9.2%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	29/257 (11.3%)		42/261 (16.1%)
Cough	27/257 (10.5%)		26/261 (10%)
Dyspnoea	21/257 (8.2%)		13/261 (5%)
Upper respiratory tract infection	20/257 (7.8%)		15/261 (5.7%)
Oropharyngeal pain	13/257 (5.1%)		6/261 (2.3%)
Skin and subcutaneous tissue disorders
Alopecia	95/257 (37%)		8/261 (3.1%)
Pruritus	21/257 (8.2%)		18/261 (6.9%)
Rash	16/257 (6.2%)		24/261 (9.2%)
Dry skin	14/257 (5.4%)		4/261 (1.5%)
Vascular disorders
Hypertension	14/257 (5.4%)		6/261 (2.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.