Breast cancer: Metastatic disease

Giuseppe Curigliano, MD, PhD

University of Milano and Istituto Europeo di Oncologia
Milano, Italia
 Disclosures

◆ Board Member : Ellipses

◆ Consultant: Lilly, Novartis, Seattle Genetics, Roche-Genentech
◆ Research grants to my Institute : MSD, Astra Zeneca
◆ Speakers bureau: Pfizer, Lilly, Novartis, Roche-Genentech, Samsung,
Celltrion
◆ Stock ownership: None
 Outline

• Metastatic ER positive/HER2 negative Breast Cancer

• Metastatic HER2 positive breast cancer
• Metastatic Triple negative Breast cancer
Treatment of ER positive/HER2 negative MBC

The Lancet 2021 3971750-1769DOI: (10.1016/S0140-6736(20)32381-3)

Endocrine sensitive disease: First line
 Endocrine sensitive disease: 1st line
N = 666
2 :1 Palbociclib

Randomization
plus
AI
PALOMA-21
placebo
plus
• HR+, HER2- ABC
AI
• Postmenopausal
• No prior systemic therapy in this setting
N = 668 abemaciclib: 150 mg BID
• If neoadjuvant or adjuvant ET Ribociclib
administered, a disease free interval of 1 :1
plus

Randomization
>12 months since completion of ET AI
• ECOG PS ≤1 MONALEESA-22
placebo
plus
AI

N = 493 abemaciclib: 150 mg BID

Abemaciclib
Primary endpoint: 2 :1
plus

Randomization
Investigator-assessed PFS AI
MONARCH-33
placebo
plus
AI

1Finn RS, et al. N Engl J Med 2016; 2Hortobagyi G, et al. N Engl J Med 2016; 3di Leo A, et al. J Clin Oncol 2017
 Endocrine sensitive disease
PALOMA 2 (2:1) MONALEESA 2 (1:1)
Median PFS Median PFS
Palbociclib + NSAI: 24.8 m
PAL+LET PCB+LET
Ribociclib + NSAI: 25.3 m
placebo + NSAI: 14.5 m
(N=444) (N=222)
placebo + NSAI: 16 m
Number of Events, 194 (44) 137 (62)
100 n (%)
Median (95% CI) 24.8 (22.1- 14.5
90 HR (95% CI): 0.58 (0.46, 0.72) p =<0.000001
PFS NR) (12.9-17.1) HR (95% CI): 0.568 (0.457, 0.704) p = 0.000000096
Progression-Free Survival, %

80 HR (95% CI); 1- 0.58 (0.46-0.72);

sided P value P<0.000001
70
60
50
40
30
20
10
0
0 3 6 9 12 15 18 21 24 27 30 33
Number of patients at Time, months
risk +
PAL 44 39 36 32 29 26 23 15
LET 69 29 10 2
4 5 0 8 5 3 8 4
PCB + 22 17 14 13 11
98 81 54 22 12 4 2
LET 2 1 8 1 6

MONARCH 3 (2:1)

Median PFS
abemaciclib + NSAI: not reached
placebo + NSAI: 14.7 m

HR (95% CI): 0.543 (0.409, 0.723) p = 0.000021

Endocrine resistant disease
 Endocrine resistant disease: 1st line
N = 521
Palbociclib
2 :1
plus

Randomization
Fulvestrant
PALOMA-31
placebo
plus
Fulvestrant
• ER+, HER2- ABC
• Pre/peri & Postmenopausal*
abemaciclib: 150 mg BID
• Progressed on prior endocrine therapy: Ribociclib
1 :1
–On or within 12 mo adjuvant plus

Randomization
–On therapy for ABC
Fulvestrant MONALEESA-32
placebo
plus
Fulvestrant

N = 669 abemaciclib: 150 mg BID

Abemaciclib
Primary endpoint: 2 :1
plus

Randomization
Investigator-assessed PFS Fulvestrant MONARCH-23
placebo
plus
*Only postmenopausal Fulvestrant

1Turner NC, et al. N Engl J Med 2015; 2Slamon D et al, J Clin Oncol 2018; 3Sledge G, et al. J Clin Oncol 2017
 Endocrine resistant disease
PALOMA 31,2 MONARCH23
HR (95% CI): 0.46 (0.36, 0.59) HR (95% CI): 0.55 (0.45, 0.68)
p =<0.0001 p =<0.001

MONALEESA 34
HR (95% CI): 0.593 (0.480, 0.732)
p =<0.001

1Turner NC, et al. N Engl J Med 2015; 2Cristofanilli M, et al. Lancet Oncol 2016; 3Sledge G, et al. J Clin Oncol 2017, 4Slamon D et al, J Clin Oncol 2018
 Overall Survival Data with CDK 4-6 inhibitors
MONALEESA-3 MONARCH 2 PALOMA-3

100 100 Palbociclib+Fulvestrant (N=347)

Overall Survival Probability (%)

Median OS=34.9 months
90 95% CI (28.8, 40.0)
80 80 Placebo+Fulvestrant (N=174)
Median OS=28.0 months
70 95% CI (23.6, 34.6)
RIB + PBO +
60 FUL FUL 60
Events/N 167/484 108/242 50
40 OS, 40
NR
median 40.0
(42.5-
(95% CI),
NR)
(37.0-NR) 30 Stratified HR=0.814
mo 95% CI (0.644, 1.029)
20 20 1-sided p=0.0429
HR (95%
0.724 (0.568-0.924) HR 0.72 HR 0.76 Unstratified HR=0.791 HR 0.81
CI) 10 95% CI (0.626, 0.999)
0 P value 0.00455 1-sided p=0.0246
0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48
Time, months 0 6 12 18 24 30 36 42 48 54
Time (Month)
No. of patients still at risk Number of patients at risk
PAL+FUL 347 321 286 247 209 165 148 126 17
Ribociclib
48447045444443642841440239738937436534833432630930028723715992 41 14 2 0 PBO+FUL 174 155 135 115 86 68 57 43 7
Placebo242233227223218213207199194187184174169159155147141134107 64 37 14 3 0 0

Sledge GW, et al. JAMA Oncol 2019;

Slamon DJ, et al. N Engl J Med 2020;382:514-524. [Epub] doi: 10.1001/jamaoncol.2019.4782. Turner NC, et al. N Engl J Med 2018;379:1926–36.
 SOLAR-1: A Phase III randomized, controlled trial
ALP 300 mg QD PO
• Men or post-menopausal + FUL 500 mg IM*
women with HR+, HER2– n=169 Primary endpoint
PIK3CA-mutant
ABC cohort R • PFS in PIK3CA-mutant cohort
• Received prior AI (n=341) PBO (locally assessed)
• Identified PIK3CA status (in + FUL 500 mg IM*
Secondary endpoints include:
archival or fresh tumor n=172
tissue) 1:1, stratified by presence of • OS (PIK3CA-mutant cohort)
liver/lung metastases and prior
• Measurable disease or CDK4/6 inhibitor treatment • PFS (PIK3CA-non-mutant cohort)
≥1 predominantly lytic
ALP 300 mg QD PO • PFS (PIK3CA-mutation in ctDNA)
bone lesion
• ECOG performance status + FUL 500 mg IM* • OS (PIK3CA-non-mutant cohort)
≤1 PIK3CA-non- n=115
mutant cohort R • ORR/CBR
(N=572)
(n=231) PBO • Safety
+ FUL 500 mg IM*
n=116

• *Fulvestrant given on Day 1 and Day 15 of the first 28-day cycle, then Day 1 of subsequent 28 day cycles.
ABC, advanced breast caner; AI, aromatase inhibitor; ALP, alpelisib; CBR, clinical benefit rate; CT, chemotherapy;
ECOG, Eastern Cooperative Oncology Group; ET, endocrine therapy; FUL, fulvestrant; IM, intramuscular;
ORR, overall response rate; OS, overall survival; PBO, placebo; PFS, progression-free survival; PO, orally; QD, daily; R, randomization.
Centrally assessed PFS in the PIK3CA-mutant cohort
Alpelisib + Placebo +
Data cut-off:
fulvestrant fulvestrant
Jun 12, 2018
(N=85) (N=88)
Number of PFS
43 (50.6) 63 (71.6)
events, n (%)
Median PFS 11.1 3.7
(95% CI) (7.3–16.8) (2.1–5.6)
HR (95% CI) 0.48 (0.32–0.71)

• Audit-based review of 50% of randomized patients in the PIK3CA-mutant cohort (n=173)

• Based on the prespecified thresholds to trigger a full BIRC review of all patient data in the PIK3CA-mutant cohort, a
full BIRC review was not required

BIRC, blinded independent review committee.

 Proof of Concept: PFS in the PIK3CA-non-mutant cohort
Proof of concept criteria were not met in the PIK3CA-non-mutant cohort

Alpelisib + Placebo +
Data cut-off:
fulvestrant fulvestrant
Dec 23, 2016
(N=115) (N=116)
Number of PFS events, n
49 (42.6) 57 (49.1)
(%)
Progression 47 (40.9) 57 (49.1)
Death 2 (1.7) 0
Censored 66 (57.4) 59 (50.9)
Median PFS 7.4 5.6
(95% CI) (5.4–9.3) (3.9–9.1)
HR (95% CI) 0.85 (0.58–1.25)
Posterior probability
79.4
HR<1, %

• Proof of concept criteria: estimated hazard ratio ≤ 0.60 and posterior probability ≥90% that HR was <1
• Statistical testing of OS was not carried out in the PIK3CA-non-mutant cohort, as proof of concept criteria were not met
• Non-mutant patients were followed up for safety alongside the PIK3CA-mutant cohort
Andrè F, et al. NEJM 2019;29:1634–57.
 Overall response rate in the PIK3CA-mutant cohort
All patients Patients with measurable disease
100 100

80 80

p=0.0002

Rate (%)
p=0.0006
Rate (%)

60 60

40 40 35.7
26.6

20 12.8 20 16.2

0 0
Overall response rate Overall response rate

Alpelisib + fulvestrant Placebo + fulvestrant

• ORR = complete response + partial response.

 Overall Survival in the PIK3CA-mutant cohort
100

• mOS was prolonged by

7.9 mo for patients in the 80

Event-free probability (%)

alpelisib + fulvestrant arm
• Final OS analysis in the 60
PIK3CA-mutant cohort
did not cross the
40
prespecified Alpelisib
+ FUL
Placebo
+ FUL
O’Brien-Fleming efficacy (n=169) (n=172)
No. events, n (%) 87 (51.5) 94 (54.7)
boundary (1-sided 20 Censored, n (%) 82 (48.5) 78 (45.3)
P≤0.0161) Median OS, mo (95% CI)
39.3
(34.1-44.9)
31.4
(26.8-41.3)
HR (95% CI) 0.86 (0.64-1.15)
0 Censoring timesb
P value (one-sided) 0.15

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54
Number of patients still at risk
Time (Months)
Alpelisib + FUL 169 162 159 156 145 141 138 133 126 122 112 111 108 103 102 94 91 85 68 56 47 35 26 19 9 4 1 0
Placebo + FUL 172 164 155 150 149 143 133 126 119 115 111 104 98 92 86 80 74 73 60 49 42 29 20 13 7 6 3 0
Full Analysis Set, PIK3CA-mutant cohort
 Overall Survival in ctDNA PIK3Ca positive
100

80

Event-free probability (%) 60

40
Alpelisib Placebo
+ FUL + FUL
(n=92) (n=94)
20 No. events, n (%) 54 (58.7) 59 (62.8)
Censored, n (%) 38 (41.3) 35 (37.2)
Median OS, 34.4 25.2
mo (95% CI) (28.7-44.9) (20.7-29.6)
0 HR (95% CI) 0.74 (0.51-1.08) Censoring timesa

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54
Time (Months)
Number of patients still at risk
Alpelisib + FUL 92 89 88 86 78 75 75 72 68 65 60 59 57 55 55 49 47 45 37 30 25 20 15 9 3 1 0 0
Placebo + FUL 94 87 82 78 77 71 65 59 56 55 53 49 45 41 36 32 28 28 25 22 20 16 13 8 3 3 2 0
Exploratory analysis; includes patients with a PIK3CA mutation in plasma ctDNA, regardless of assignment to
PIK3CA mutant or PIK3CA non-mutant cohort per tissue
ctDNA, circulating tumour DNA.
aDate of censoring is defined as the last contact date for OS.
 Time to first chemotherapy
100

80
• A median TTC delay of 8.5 months was observed
Event-free probability (%)
for patients in the alpelisib + fulvestrant arm
60

40
Alpelisib Placebo
+ FUL + FUL
(n=169) (n=172)
20 No. events, n (%) 95 (56.2) 109 (63.4)
Censored, n (%) 74 (43.8) 63 (36.6)
Median TTC, 23.3 14.8
mo (95% CI) (15.2-28.4) (10.5-22.6)
Censoring times
0 HR (95% CI) 0.72 (0.54-0.95)
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54

Number of patients still at risk

Time (Months)
Alpelisib + FUL 169 160 147 131 116 103 93 85 80 77 71 69 64 55 53 49 48 44 34 29 26 20 12 10 4 1 0 0
Placebo + FUL 172 156 118 107 99 86 75 68 64 61 60 55 47 44 41 38 34 31 27 20 17 14 10 6 4 4 2 0
Post hoc exploratory analysis, PIK3CA-mutant cohort
TTC, time to chemotherapy.
aTime to chemotherapy is defined as time from randomisation for first chemotherapy, censored at last contact date or death.
 Safety
• After a median follow-up of 42.4 months, safety profile remains consistent1
Alpelisib + FUL (n=284) Placebo + FUL (n=287)
AEs ≥20% in Either Arm, % All-Grade Grade 3 Grade 4 All-Grade Grade 3 Grade 4
Any AE 282 (99.3) 187 (65.8) 35 (12.3) 267 (93.0) 90 (31.4) 17 (5.9)
Hyperglycaemia 184 (64.8) 94 (33.1) 11 (3.9) 27 (9.4) 2 (0.7) 1 (0.3)
Diarrhoea 169 (59.5) 20 (7.0) 0 47 (16.4) 2 (0.7) 0
Nausea 133 (46.8) 8 (2.8) 0 65 (22.6) 1 (0.3) 0
Decreased appetite 103 (36.3) 2 (0.7) 0 30 (10.5) 1 (0.3) 0
Rash 103 (36.3) 28 (9.9) 0 20 (7.0) 1 (0.3) 0
Vomiting 81 (28.5) 2 (0.7) 0 29 (10.1) 1 (0.3) 0
Weight decreased 79 (27.8) 15 (5.3) 0 7 (2.4) 0 0
Fatigue 72 (25.4) 10 (3.5) 0 51 (17.8) 3 (1.0) 0
Stomatitis 71 (25.0) 7 (2.5) 0 20 (7.0) 0 0
Asthenia 64 (22.5) 7 (2.5) 0 39 (13.6) 0 0
Alopecia 58 (20.4) 0 0 7 (2.4) 0 0
Safety Set

• AESI of rasha was observed in 153 (53.9%) and 27 (9.4%) of patients in the alpelisib + fulvestrant vs placebo +
fulvestrant arms, respectively; the majority of these events were grade 1 or grade 2
 Alpelisib following CDK 4-6 inhibitors
Goal: In the post-CDKi setting, assess the efficacy and safety of alpelisib + ET (fulvestrant or letrozole)
in patients with PIK3CA-mutated HR+, HER2– ABC

Patients who received CDKi + AI

as immediate prior treatment (N=112)b Primary endpoint
Men or pre-/postmenopausala (Cohort A)
women with HR+, HER2– ABC with • Proportion of patients alive without PD at
Alpelisib 300 mg oral QD + fulvestrant 500 mgc 6 months (RECIST v1.1) in each cohort
a PIK3CA mutation
• Secondary endpoints include
• Last line of prior therapy: CDKi + Patients who received CDKi + fulvestrant
as immediate prior treatment (N=112) (assessed in each cohort)
ET, systemic chemotherapy or ET
(Cohort B) • PFS
• ECOG PS ≤2 Alpelisib 300 mg oral QD + letrozole 2.5 mgd • PFS2
• Measurable disease (per RECIST • ORR, CBR, DOR
v1.1) or ≥1 predominantly lytic
bone lesion Patients who progressed on/after AI and received chemotherapy or • OS
ET as immediate prior treatment (N=112)
• Safety
(Cohort C)
Alpelisib 300 mg oral QD + fulvestrant 500 mgc

Treatment crossover between cohorts is not permitted

aMen in the letrozole cohort and premenopausal women also received goserelin 3.6 mg SC every 28 days or leuprolide 7.5 mg IM every 28 days for adequate gonadal suppression. bEnrollment in each cohort continued until at least 112 patients with a centrally confirmed PIK3CA mutation was reached.
c IMon D1 and D15 of Cycle 1 and D1 for all other cycles thereafter. dOral QD.
ABC, advanced breast cancer; AI, aromatase inhibitor; CDKi, cyclin-dependent kinase inhibitor; ECOG PS, Eastern Cooperative Oncology Group performance status; ET, endocrine therapy; CBR, clinical benefit rate; D, day; DOR, duration of response; IM, intramuscularly; ORR, overall response rate; OS, overall survival; PD, progressive
disease; PFS, progression-free survival; PFS2, PFS on next-line treatment; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; RECIST, Response Evaluation Criteria In Solid Tumors; SC, subcutaneously; QD, once daily.
 Alpelisib following CDK 4-6 inhibitors
Prior CDKi + AI 1.0
Endpoint (Cohort A) 0.9 Censoring times
0.8 Prior CDKi + AI
(n=121) cohort (n=121)
0.7

Probability
No of events: 72
0.6
0.5
Primary endpoint: Patients who were 50.4% 0.4
(n=61;
alive without disease progression at 6 mo 0.3
95% CI, 41.2-59.6)
0.2
0.1
0.0
7.3 mo 0 2 4 6 8 10 12 14 16 18 20 22 24
Secondary endpoint: Median PFS [n=72 (59.5%) with Time, months
No. of patients still at risk
event]; 95% CI, 5.6-8.3)
Prior CDKi + AI 121 95 77 54 40 15 8 5 4 1 1 1 0

The primary endpoint for the prior CDKi + AI cohort was met (lower bound of 95% CI was > 30%),
with 50.4% of patients alive without disease progression at 6 months
• In SOLAR-1, 44.4% of patients in the PIK3CA-mutant cohort with prior CDKi treated with alpelisib plus fulvestrant
were alive without disease progression at 6 months

AI, aromatase inhibitor; CDKi, cyclin-dependent kinase inhibitor; CI, confidence interval; PFS, progression-free survival; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha.
 Alpelisib following CDK 4-6 inhibitors
Prior CDKi + AI (Cohort A)
Response rates, n (%)
Study Treatment: Alpelisib + Fulvestrant
All patients with centrally confirmed Patients with measurable disease
PIK3CA mutation at baseline
Best overall response (n=121) (n=100)
Complete response (CR) 0 0
Partial response (PR) 21 (17.4) 21 (21.0)
Neither CR nor PDa (NCR/NPD) 16 (13.2) 0
Stable disease (SD) 55 (45.5) 55 (55.5)
Progressive disease (PD)b 14 (11.6) 11 (11.0)
Unknown (UNK) 15c (12.4) 13 (13.0)
Overall response rate (ORR: CR + PR) 21 (17.4); 95% CI (11.1-25.3) 21 (21.0); 95% CI (13.5-30.3)
Clinical benefit rate (CBR: CR + PR +
55 (45.5); 95% CI (36.4-54.8) 42 (42.0); 95% CI (32.2-52.3)
SD+NCR/NPD ≥24 wk)

aRefers to presence of lesions not fulfilling criteria for target lesions at baseline or abnormal nodal lesions (ie,≥10 mm), unless there is unequivocal progression of the non-target lesions (PD) or it is not possible to determine progression unequivocally (UNK).
bRefers to neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions that would qualify for PD.
c11 patients had no valid post-baseline tumor assessment; 1 patient was coded as SD by investigator too early since that occurred before 6 weeks of the start date of study treatment; 2 patients had started the new antineoplastic treatment before first post-

baseline tumor assessment; 1 patient was coded as PD by investigator too late since the algorithm has shown PD.
 Alpelisib following CDK 4-6 inhibitors
BYLieve, (127.3) SOLAR-1
100% 100%
Prior CDKi + AI (Cohort A) Alpelisib + Fulvestrant1
Alpelisib + Fulvestrant
80% 80%

60% 60%

40% 40%
Best % Change From Baseline

Best % Change From Baseline

*** *******
(Measurable Lesions)

(Measurable Lesions)
20% 20%

0% 0%

–20% –20%

–40% –40%

–60% –60%

–80% –80% BYLieve,

Prior CDKi + AI
–100% (Cohort A) SOLAR-1
–100%
(n=87)a (n=116)1
Decrease in best % change from
SOLAR-1 data cutoff date: June 12, 2018; BYLieve data cutoff date: December 17, 2019.
70.1% 75.9%
baseline
*Best percentage change in sum of diameters per investigator assessment, for patients with measurable disease at baseline.
Increase/zero change in best %
aPatients with missing best percentage change or those with best percentage change in target lesion but overall response of Unknown are 26.4% 18.1%
excluded' change from baseline
1. Reprinted from Juric D, et al. SABCS 2018. Abstract GS3-08 (oral).
Oral SERDs

Journal of Clinical Oncology 39, no. 12 (April 20, 2021) 1360-1370.

Treatment of HER2 positive MBC

The Lancet 2021 3971750-1769DOI: (10.1016/S0140-6736(20)32381-3)

Trastuzumab Deruxtecan (DS-8201a/T-DXd)
Structure and Mechanism of Action
Payload with a different mechanism of
action

High potency of payload

Payload with short systemic half-life

Bystander effect

Stable linker-payload

Tumor-selective cleavable linker

High drug-to-antibody ratio

Iwata et al. ASCO 2018

 DESTINY-Breast01 Study Design:
An Open-Label, Multicenter, Phase 2 Study
PART 1 PART 2
Population
PK Stage Dose-Finding Stage Continuation Stage
• ≥18 years of age (n=65) (n=54) (n=134)
• Unresectable and/or
metastatic BC
T-DM1 R 5.4 mg/kg
• HER2-positive (centrally Resistant/Refractory 1:1:1 (n=22)
confirmed on archival (n=249) 5.4 mg/kg
(n=28) PART 2a
tissue) 6.4 mg/kg R
(n=22) 1:1 5.4 mg/kg
• Prior T-DM1 6.4 mg/kg (n=130)
(n=26)
• Excluded patients with 7.4 mg/kg
history of significant ILD (n=21)

• Stable, treated brain T-DM1 PART 2b

metastases were Intolerant 5.4 mg/kg
allowed (n=4) (n=4)

184 patients
Endpoints Data Cutoff: August 1, 2019 enrolled at 5.4 mg/kg
• Primary: confirmed ORR by independent central imaging facility review • 79 patients (42.9%) are ongoing
per RECIST v1.1 • 105 patients (57.1%) discontinued, primarily for progressive disease (28.8%)
• Secondary: investigator-assessed ORR, DCR, DOR, CBR, PFS, OS, PK and
safety
Modi S et al. N Engl J Med. 2020 Feb 13;382(7):610-621.
 Patient Baseline Characteristics (cont’d)
Median prior lines of cancer therapy: 6 (range 2-27)

Patients, %
Prior Treatmenta T-DXd 5.4 mg/kg (N=184)

Trastuzumab 100
T-DM1 100
Pertuzumab 65.8
Other anti-HER2 therapies 54.3
Hormone therapy 48.9
Other systemic therapy 99.5

aTherapies for locally advanced or metastatic breast cancer, including hormone therapy.

Modi S et al. N Engl J Med. 2020 Feb 13;382(7):610-621.

 Primary Endpoint: Objective Response Rate
Patients
Intent-to-treat analysis T-DXd 5.4 mg/kg (N = 184)
60.9% (n = 112)
Confirmed ORR by ICR
(95% CI, 53.4%-68.0%)
CR 6.0% (n = 11)
PR 54.9% (n = 101)
SD 36.4% (n = 67)
PD 1.6% (n = 3)
Not evaluable 1.1% (n = 2)
DCR 97.3% (95% CI, 93.8%-99.1%)
CBR 76.1% (95% CI, 69.3%-82.1%)
Duration of response, median 14.8 months (95% CI, 13.8-16.9)
• Median time to response was 1.6 months (95% CI, 1.4-2.6 months)
CBR, clinical benefit rate (SD for ≥6 mo + CR + PR); CR, complete response; DCR, disease control rate (CR + PR + SD); ICR, independent central review; ORR, objective response rate (CR + PR); PD, progressive
disease; PR, partial response; SD, stable disease.

Modi S et al. N Engl J Med. 2020 Feb 13;382(7):610-621.

 Best Change in Tumor Size
40
n=168
Best % Change From Baseline in the Sum
of Diameters of Measurable Tumors

20

-20

-40

-60 Confirmed ORR: 60.9%a

(95% CI, 53.4%–68.0%)
-80 11 CRs

-100

By independent central review.

The line at 20% indicates progressive disease; the line at −30% indicates partial response.
a Includes all patients who received T-DXd 5.4 mg/kg (intent-to-treat analysis; N=184).

Modi S et al. N Engl J Med. 2020 Feb 13;382(7):610-621.

 Progression-Free and Overall Survival
Progression-Free Survival Overall Survival
Median: 16.4 months (95% CI, 12.7-NE) Median: Not reached (95% CI, NE-NE)
Probability of Progression-Free Survival

1.0 1.0

0.8 0.8

Probability of Survival
0.6 0.6

0.4 0.4

0.2 0.2
Censored: 68.5% Censored: 86.4%
Events: 31.5% Events: 13.6%
0.0 0.0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Months Months
No. at risk: 184 182 174 155 153 135 121 107 103 94 69 54 38 17 11 10 9 4 3 1 0 No. at risk: 184 183 182 179 174 171 167 161 155 147 133 101 66 36 21 16 12 9 8 4 0

• Median follow-up, 11.1 months (range, 0.7-19.9 months)

• Median PFS in the 24 patients with brain metastases was 18.1 months (95% CI, 6.7-18.1 months)

Patients who received T-DXd 5.4 mg/kg.

CI, confidence interval; NE, not estimable.

Modi S et al. N Engl J Med. 2020 Feb 13;382(7):610-621.

 Adverse Events of Special Interest: Interstitial Lung Disease
Patients who received T-DXd 5.4 mg/kg (N=184)
Preferred Term, Any
n (%) Grade/
Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Total
Interstitial
5 (2.7) 15 (8.2) 1 (0.5) 0 4 (2.2) 25 (13.6)
lung disease
Drug related; ILD was determined by the Independent ILD Adjudication Committee based on 44 preferred
terms.
Among the 25 total events:
• Median time to investigator-reported onset was 193 days (range, 42-535 days)
• 17 of 20 patients with grade ≥2 ILD received corticosteroids
• 7 patients recovered, 2 were recovering, 12 were either outcome unknown or not followed until
resolution, and 4 died
• Of the 4 fatal cases, onset was from 63-148 days, 3 received steroids as part of treatment, and
death occurred 9-60 days after diagnosis

Recommendations: Monitor for symptoms. Hold T-DXd and start steroids as soon as ILD is suspected

ILD, interstitial lung disease.

Modi S et al. N Engl J Med. 2020 Feb 13;382(7):610-621.

 Trastuzumab duocarmazine: SYD-985

• Trastuzumab duocarmazine (also known as SYD985) is a novel HER2-

targeting antibody–drug conjugate comprising the monoclonal IgG1
antibody trastuzumab covalently bound to a linker drug containing
duocarmycin.
• The linker drug contains a cleavable linker and the prodrug seco-
duocarmycin–hydroxybenzamide–azaindole (seco-DUBA). After binding to
HER2 and internalisation the linker is cleaved in the lysosome by proteases
that release the active toxin (DUBA). The active toxin alkylates DNA,
resulting in DNA damage in both dividing and non-dividing cells and
ultimately cell death.

Banerji U et al. Lancet Oncol. 2019 Jun 27. pii: S1470-2045(19)30328-6.

 Trastuzumab duocarmazine: Activity

• Overall, 86.3% of subjects experienced tumor shrinkage

• Confirmed ORR* in the overall population is 49.3%
Banerji U et al. Lancet Oncol. 2019 Jun 27. pii: S1470-2045(19)30328-6.
 HER2CLIMB: Tucatinib
• Patients with LA or metastatic
HER2-positive MBC
• Central HER2 testing
• Prior treatment with taxane,
trastuzumab, pertuzumab, and
T-DM1 in any setting Tucatinib + capecitabine +
• No prior treatment with
neratinib, afatinib, or any trastuzumab
experimental EGFR/HER2 TKI R (n = 320)
• No prior lapatinib in previous 2:1 Treat until PD,
12 months unacceptable
• No prior capecitabine for MBC toxicity
• Patients with untreated or Placebo + capecitabine +
progressive brain metastases
eligible trastuzumab
(n = 160)
(N = 480)

ClinicalTrials.gov. NCT02614794.
KEY BASELINE DEMOGRAPHICS AND DISEASE CHARACTERISTICS
Total Population, N=612
TUC+Tras+Cape Pbo+Tras+Cape
Characteristic, n (%) n=410 n=202
Female 407 (99) 200 (99)
Age (years), median (range) 55.0 (22, 80) 54.0 (25, 82)
0 204 (50) 94 (47)
ECOG performance status
1 206 (50) 108 (54)
Stage IV at initial diagnosis 143 (35) 77 (39)
ER and/or PR-positive 243 (60) 127 (63)
Hormone receptor status
ER and PR-negative 161 (40) 75 (37)
Prior lines of therapy, median Overall 4.0 (2, 14) 4.0 (2,17)
(range) Metastatic setting 3.0 (1, 14) 3.0 (1, 13)
Presence/history of brain metastases 198 (48) 93 (46)
Treated, stable 80 (40.4) 37 (39.8)
Untreated 44 (22.2) 22 (23.7)
Treated, progressing 74 (37.4) 34 (36.6)

Baseline characteristics were balanced between endpoint populations and treatment arms
PROGRESSION-FREE SURVIVAL IN THE PRIMARY ENDPOINT POPULATION
Events HR
N=480 (95% CI) P Value Risk of progression or death was
TUC+Tras+Cape 178/320 0.54 <0.0000 reduced by 46% in the primary
(0.42, 0.71) 1 endpoint population
Pbo+Tras+Cape 97/160
63% One-year PFS (95% CI):
TUC+Tras+Cape Pbo+Tras+Cape
Median
33% 12%
46% (27, 40) (6, 21)
33%
Median PFS (95% CI):
7.8 months 5.6 months
12% (7.5, 9.6) (4.2, 7.1)

Prespecified efficacy boundary for PFS:

P=0.05
Data cut off: Sep 4, 2019
OVERALL SURVIVAL IN THE TOTAL STUDY POPULATION
Events HR
N=612 (95% CI) P Value
Risk of death was reduced
TUC+Tras+Cape 130/410 0.66 0.00480
(0.50, 0.88) by 34% in the total
76% Pbo+Tras+Cape 85/202
population
Two-year OS (95% CI):
62%
Median
TUC+Tras+Cape Pbo+Tras+Cape
45% 45% 27%
(37, 53) (16, 39)

27% Median OS (95% CI):

21.9 months 17.4 months

(18.3, 31.0) (13.6, 19.9)

Prespecified efficacy boundary for OS

(P=0.0074) was met at the first interim
analysis.
Data cut off: Sep 4, 2019
PROGRESSION-FREE SURVIVAL FOR PATIENTS WITH BRAIN METASTASES
Events HR Risk of progression or death in
N=291 (95% CI) P Value
patients with brain metastases
TUC+Tras+Cape 106/198 0.48 <0.00001
was reduced by 52% in the total
Pbo+Tras+Cape 51/93 (0.34, 0.69)
population
60%
One-year PFS (95% CI):
Median
TUC+Tras+Cape Pbo+Tras+Cape
25% 0%
34% (17, 34)
25%
Median PFS (95% CI):
7.6 months 5.4 months
0% (6.2, 9.5) (4.1, 5.7)
Prespecified efficacy boundary for PFSBrainMets
(P=0.0080) was met at the first interim analysis.
Data cut off: Sep 4, 2019
 CONFIRMED OBJECTIVE RESPONSE RATE IN THE TOTAL STUDY POPULATION
Patients with Measurable Disease
Confirmed Objective Response Rate N=511
(RECIST 1.1, BICR) TUC+Tras+Cape Pbo+Tras+Cape
* n=340 n=171
Response, n (%)
Best Overall Responsea
Complete Response (CR) 3 (1) 2 (1)
Partial Response (PR) 135 (40) 37 (22)
Stable Disease (SD) 155 (46) 100 (59)
Progressive Disease (PD) 27 (8) 24 (14)
Not Evaluable 0 1 (1)
Not Availableb 20 (6) 7 (4)
Time to Response (months), 1.4 1.4
median (min, max) (1.1, 9.7) (1.2, 15.7)
Clinical Benefit Rate
*Stratified Cochran-Mantel-Haenszel P value for ORR
60% 38%
(CR + PR + SD >6 months)
a. Confirmed best overall response assessed per RECIST 1.1
b. Patients with no post-baseline response assessments
MOST COMMON ADVERSE EVENTS (≥20% IN THE TUCATINIB ARM)
100
90
Grade Grade Grade
80 1 2 ≥3
70 TUC + Tras + Cape
60
Frequency

Pbo + Tras + Cape

50
40
30
20
10
0

PPE: palmar-plantar erythrodysesthesia, AST: aspartate transaminase, ALT: alanine transaminase

Treatment of triple negative MBC

The Lancet 2021 3971750-1769DOI: (10.1016/S0140-6736(20)32381-3)

 TNBC: An heterogeneous disease

• Invasive Ductal Carcinoma high grade

Poor
• Invasive Lobular Carcinoma high grade, pleomorphic prognosis
• High grade neuroendocrine
• Metaplastic, high grade
• Myoepithelial carcinoma
• Medullary
• Apocrine
• Adenoid-cystic
• Metaplastic, low grade Good
prognosis
 Triple negative disease

Subtype Gene expression profile Clinical

Basal-like 1 high Ki-67; DNA damage response BRCA-associated
Basal-like 2 GF pathways Higher pCR
Immunomodulatory Immune genes
Mesenchymal Cell motility Lower DDFS
Mesenchymal stem-like Cell motility; claudin-low
Luminal androgen receptor Steroid pathways Apocrine features,
higher LRF; PI3Kmut
 BRCA mutated TNBC

Subtype Gene expression profile Clinical

Basal-like 1 high Ki-67; DNA damage response BRCA-associated
Basal-like 2 GF pathways Higher pCR
Immunomodulatory Immune genes
Mesenchymal Cell motility Lower DDFS
Mesenchymal stem-like Cell motility; claudin-low
Luminal androgen receptor Steroid pathways Apocrine features,
higher LRF; PI3Kmut
 • gBRCAm mBC OlympiAD Primary endpoint
• TNBC or HER2-negative, ER/PR positive
FSI May 20143
• ≤2 prior chemotherapy lines for mBC • PFS (RECIST 1.1,
Global Study in 19 Independent Review)
• Previous treatment must include countries and
anthracycline and taxane approximately 141
• Hormone receptor positive (HR+) disease sites1 Secondary endpoints
progressed on ≥1 endocrine therapy, or not Olaparib • OS
suitable
300mg*po bid • PFS2
• If patients have received platinum therapy Randomise 2:1
there should be: N=3024 • ORR
• No evidence of progression during Treatment of • PFS, PFS2 and OS
treatment in the advanced setting Physician’s based on Myriad
Stratification by2
Choice (TPC) gBRCAm status
• At least 12 months since (neo)adjuvant • Prior chemotherapy
treatment and randomisation regimens for metastatic Capecitabine, • HRQoL (EORTC-QLQ-
• ECOG PS 0-1
breast cancer eribuline and C30)
• Hormonal receptor (HR) vinorellbine • Safety and
• At least one lesion that can be assessed by status
RECIST v1.1 • Prior platinum therapy tolerability

M=metastatic breast cancer, HER2=human epidermal growth factor 2, TNBC=triple negative breast cancer, TPC=treatment of physician’s choice, OS=overall survival, PFS=progression-free survival,
PFS2=progression-free survival 2, ORR=objective response rate, HRQoL=health-related quality of life, FSI=first subject in, RECiST= Response Evaluation Criteria in Solid Tumors, ER=oestrogen receptor,
PR=progresterone receptor, ECOG PS= Eastern Cooperative Oncology Group Performance Status, gBRCAm=germline BRCA mutation; po=oral
1. https://clinicaltrials.gov/ct2/show/NCT02000622; 2. Robson et al. Poster OT1-1-04, San Antonio Breast Cancer Symposium 2014; 3. AZ data on file (2017),
4. Robson et al. N Engl J Med. 2017; 377:523-533
 Progression free survival
Probability of progression-free survival

1.0 Olaparib TPC

Olaparib 300 mg bd (N=205)
n 205 97
0.9 TPC (N=97)
Events (%) 163 (79.5%) 71 (73.2%)
0.8
0.7 Median (m) 7.0 4.2

0.6 HR = 0.58
95 % CI (0.43, 0.80)
p=0.0009
0.5
0.4 PFS free at 6m (%) 54.1 32.9

0.3 PFS free at 12m (%) 25.9 15.0

0.2 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Time from randomisation (months)
Number of patient’s at risk 0.1
Olaparib 205201177159154129107100 94 73 69 61 40 36 23 21 21 11 11 11 4 3 3 2 2 1 1 1 0 Median PFS was improved by 69% with
TPC 0.0
97 88 83 46 44 29 25 24 21 13 11 11 8 7 4 4 4 1 1 1 1 1 1 1 1 0 0 0 0
olaparib treatment compared to
standard of care chemotherapy
Robson et al. N Engl J Med. 2017; 377:523-533
 Response rate
Olaparib TPC

Response Evaluable Population, n 167 66

ORR, n (%) 100 (59.9) 19 (28.8)

Complete Response, n (%) 15 (9.0) 1 (1.5)

Partial Response, n (%) 85 (51.0) 18 (27.3)

Median Duration of Response, months

6.4 (2.9-9.7) 7.1 (3.2-12.2)
(95%CI)

Median Time to Onset of Response, days 47 45

Robson et al. N Engl J Med. 2017; 377:523-533

 EMBRACA: Study Design
Patients with locally
advanced or metastatic Primary endpoint
HER2-negative breast Talazoparib • Progression-free survival by
cancer and a germline 1 mg PO daily RECIST by blinded central
review
BRCA1 or BRCA2 Treatment (21-day cycles)
mutation*† continues until progression or
Key secondary efficacy
R unacceptable toxicity endpoints
2:1 • Overall survival (OS)
Stratification factors: • Objective response rate (ORR)
Physician's choice by investigator
• Number of prior chemo
of therapy (PCT)‡: • Safety
regimens (0 or ≥1)
capecitabine,
• TNBC or hormone eribulin, Exploratory endpoints
receptor positive (HR+) gemcitabine, • Duration of response (DOR)
or vinorelbine for objective responders
• History of CNS mets or
• Quality of life (QoL; EORTC
no CNS mets QLQ-C30, QLQ-BR23)

*Additional inclusion criteria included: no more than 3 prior cytotoxic chemotherapy regimens for locally advanced or
metastatic disease;
prior treatment with a taxane and/or anthracycline unless medically contraindicated.
†HER2-positive disease is excluded.
‡Physician's choice of therapy must be determined prior to randomization.

CNS=central nervous system; EORTC=European Organisation for Research and Treatment of Cancer; HER2=human epidermal
growth factor receptor 2; mets=metastases; PO= by mouth; QLQ-BR23=Quality of Life Questionnaire breast cancer module;
QLQ-C30=Quality of Life Questionnaire Core 30; R=randomized; RECIST=Response Evaluation Criteria In Solid Tumors version 1.1;
TNBC=triple-negative breast cancer.
Litton J, et al. N Engl J Med 2018; 379:753-763.
 Progression free survival

Litton J, et al. N Engl J Med 2018; 379:753-763.

 Overall survival

Litton J, et al. N Engl J Med 2018; 379:753-763.

 Response rate

Litton J, et al. N Engl J Med 2018; 379:753-763.


Patient Population
• Advanced HER2– breast cancer
• Germline BRCA1 or BRCA2
mutation
• ≤2 prior lines cytotoxic therapy for
metastatic disease
• ≤1 prior lines of platinum; no
progression ≤12 months of
completing
Stratification Factors
• Hormone Receptor Expression
• Prior Platinum
• CNS Metastasis
BROCADE 3
Veliparib +
Treat to progression:
Carboplatin/paclitaxel
If carboplatin and paclitaxel
2:1 discontinued prior to
Randomization progression, dosing of
veliparib/placebo increased
N=513 to 300mg BID continuous,
and then 400mg BID if Optional open-
Placebo +
tolerated label crossover to
Carboplatin/paclitaxel
veliparib
Primary Endpoint:
Investigator-assessed PFS per RECIST 1.1
21-Day Cycles:
• Carboplatin (C): AUC 6 on Day 1
• Paclitaxel (P): 80 mg/m2 on Days 1, 8, 15
• Veliparib or Placebo: 120mg BID on Days -2 to 5
 BROCADE 3

HR 0.705 Veliparib + C/P Placebo + C/P

[95% CI 0.566-0.877], p = 0.002
PFS by Inv. PFS Events, n/N 217/337 132/172
Median PFS, months 14.5 12.6
Patients Free from Disease
Progression or Death (%)

[95% CI] [12.5, 17.7] [10.6, 14.4]

Months from Randomization

C/P: Carboplatin and Paclitaxel

 BROCADE 3
Secondary Endpoint: Overall Survival (Interim Analysis)
Veliparib + C/P Placebo + C/P
HR = 0.945 (95% CI 0.729-1.225, p = 0.666)
Interim OS OS Events, n/N 167/337 87/172
Median OS, months 33.5 28.2
[95% CI] [27.6, 37.9] [24.7, 35.2]

HR 0.945
[95% CI 0.729-1.225], p = 0.666

44% of ITT subjects randomized to placebo + C/P elected open-

C/P: Carboplatin and Paclitaxel label veliparib as 1st subsequent therapy (crossover)
 BROCADE 3

Veliparib +C/P Placebo + C/P

(N = 337) (N = 172)

Clinical Benefit Rate (at 24 weeks), % 90.7 93.2

[95%CI] [87.9, 92.9] [89.5, 95.7]

Objective Response Rate (CR+PR), % 75.8 74.1

[95% CI] [70.4, 80.6] [66.1, 81.1]

Clinical Benefit Rate: CR, PR, or SD per RECIST v1.1

Objective Response: Investigator-assessed RECIST v1.1
C/P: Carboplatin and Paclitaxel
 BROCADE 3
HR 0.760 Veliparib + C/P Placebo + C/P
[95% CI 0.603-0.959], p = 0.020 *
PFS2 PFS2 Events, n/N 196/337 114/172
HR = 0.760 (95% CIMedian
0.603, 0.959, p =21.3
PFS2,
0.020 nominal)
17.4
months [95% CI] [19.8, 25.1] [16.0, 20.0]

* P value nominal PFS2 defined as time from randomization until

C/P: Carboplatin and Paclitaxel disease progression on subsequent therapy or death
 Carboplatin in BRCA mutant
ER-, PgR-/unknown & HER2- or known BRCA1/2
Metastatic or recurrent locally advanced

Exclusions include:
• Adjuvant taxane in ≤12 months
• Previous platinum treatment
• Non-anthracyclines for MBC

A Priori subgroup analyses:

• BRCA1/2 mutation RANDOMISE
• (1:1)
Basal-like subgroups (PAM50 and IHC)
• Biomarkers of HRD
Tutt A et al, 2108

Carboplatin (C) Docetaxel (D)

AUC 6 q3w, 6 cycles n-376 100mg/m2 q3w, 6 cycles

On progression, BRCA1/2 = On progression,

crossover if appropriate 9%/12% crossover if appropriate

Docetaxel (D) Carboplatin (C)

100mg/m2 q3w, 6 cycles AUC 6 q3w, 6 cycles
 Carboplatin in non BRCA mutant
Randomised treatment - all
% with OR at cycle 3 or 6 (95% CI)
patients (N=376)
0 20 40 60 80 100

59/188
Carboplatin
(31.4%) Absolute difference (C-D)
-4.2% (95% CI -13.7 to 5.3)
67/188
Docetaxel Exact p = 0.44
(35.6%)

Crossover treatment - all

patients (N=182) % with OR at cycle 3 or 6 (95% CI)
0 20 40 60 80 100

Carboplatin 21/92*
(Crossover=Docetaxel) (22.8%) Absolute difference (D-C)
-2.8% (95% CI -15.2 to 9.6)
Docetaxel 23/90*
(Crossover=Carboplatin) (25.6%) Exact p = 0.73

Tutt, 2018
 Carboplatin in BRCA mutant
Germline BRCA 1/2 Percentage with OR at cycle 3 or 6 (95% CI)
Mutation (n=43) 0 10 20 30 40 50 60 70 80 90 100

17/25
Carboplatin
(68.0%)

6/18 Absolute difference (C-D)

Docetaxel
(33.3%)
34.7% (95% CI 6.3 to 63.1)
No Germline BRCA 1/2 Exact p = 0.03
Mutation (n=273)
Percentage with OR at cycle 3 or 6 (95% CI)
0 10 20 30 40 50 60 70 80 90 100

Carboplatin
36/128 Absolute difference (C-D)
(28.1%)
-8.5% (95% CI -19.6 to 2.6)
Exact p = 0.16
Docetaxel 53/145
(36.6%)

Interaction: randomised treatment & BRCA 1/2 status: p = 0.01

60
 PDL-1 positive

Subtype Gene expression profile Clinical

Basal-like 1 high Ki-67; DNA damage response BRCA-associated
Basal-like 2 GF pathways Higher pCR
Immunomodulatory Immune genes
Mesenchymal Cell motility Lower DDFS
Mesenchymal stem-like Cell motility; claudin-low
Luminal androgen receptor Steroid pathways Apocrine features,
higher LRF; PI3Kmut
 Atezolizumab and nab-Paclitaxel in mTNBC
Key IMpassion130 eligibility criteriaa: Atezo + nab-P arm:
Atezolizumab 840 mg IV
• Metastatic or inoperable locally advanced TNBC
‒ On days 1 and 15 of 28-day cycle
‒ Histologically documentedb
+ Nab-paclitaxel 100 mg/m2 IV
• No prior therapy for advanced TNBC ‒ On days 1, 8 and 15 of 28-day cycle
‒ Prior chemo in the curative setting, including taxanes,
allowed if TFI ≥ 12 mo R Double blind; no crossover permitted
RECIST v1.1 PD
1:1 or toxicity
• ECOG PS 0-1
Stratification factors: Plac + nab-P arm:
Placebo IV
• Prior taxane use (yes vs no)
‒ On days 1 and 15 of 28-day cycle
• Liver metastases (yes vs no)
+ Nab-paclitaxel 100 mg/m2 IV
• PD-L1 status on IC (positive [≥ 1%] vs negative [< 1%])c ‒ On days 1, 8 and 15 of 28-day cycle

• Co-primary endpoints were PFS and OS in the ITT and PD-L1+ populationsd
– Key secondary efficacy endpoints (ORR and DOR) and safety were also evaluated

IC, tumour-infiltrating immune cell; TFI, treatment-free interval. a ClinicalTrials.gov: NCT02425891. b Locally evaluated per ASCO–College of American Pathologists (CAP)
guidelines. c Centrally evaluated per VENTANA SP142 IHC assay (double blinded for PD-L1 status). d Radiological endpoints were investigator assessed
(per RECIST v1.1).
Schmid P, et al. N Engl J Med. 2018 Nov 29;379(22):2108-2121
 Patients
Atezo + nab-P Plac + nab-P Atezo + nab-P Plac + nab-P
Characteristic (N = 451) (N = 451) Characteristic (N = 451) (N = 451)
Median age (range), y 55 (20-82) 56 (26-86) Metastatic disease, n (%) 404 (90%) 408 (91%)
Female, n (%) 448 (99%) 450 (100%) No. of sites, n (%)d
Race, n (%)a 0-3 332 (74%) 341 (76%)
White 308 (68%) 301 (67%) ≥4 118 (26%) 108 (24%)
Asian 85 (19%) 76 (17%) Site of metastatic disease, n (%)
Black/African American 26 (6%) 33 (7%) Lung 226 (50%) 242 (54%)
Other/multiple 20 (4%) 26 (6%) Bone 145 (32%) 141 (31%)
ECOG PS, n (%)b,c Liver 126 (28%) 118 (26%)

0 256 (57%) 270 (60%) Brain 30 (7%) 31 (7%)

1 193 (43%) 179 (40%) Lymph node onlyd 33 (7%) 23 (5%)

Prior (neo)adjuvant PD-L1+ (IC), n (%) 185 (41%) 184 (41%)
284 (63%) 286 (63%)
treatment, n (%)
Prior taxane 231 (51%) 230 (51%) Data cutoff: 17 April 2018. a Race was unknown in 12 patients in the Atezo + nab-P arm and 15 in
the Plac + nab-P arm. b Of n = 450 in each arm. c ECOG PS before start of treatment was 2 in 1
Prior anthracycline 243 (54%) 242 (54%) patient per arm. d Of n = 450 in the Atezo + nab-P arm and n = 449 in the Plac + nab-P arm arm.

Schmid P, et al. N Engl J Med. 2018 Nov 29;379(22):2108-2121

 Secondary efficacy endpoints
70 ITTa PD-L1+b
56% 59%
60

50
46% 43% • Numerically higher and more durable responses
ORR (%)

were seen in the Atezo + nab-P arm

40
49% – Differences were not significant based on α
49%
30 level = 0.1% (ITT: P = 0.0021; PD-L1+: P =
44% 42% 0.0016)
20

PR: 10 • The CR rate was higher in the Atezo

7% 10% + nab-P arm vs the Plac + nab-P arm
CR: 0
Atezo
ITT A-+ Plac
ITT+ P-
nab- Atezo +A- PD-L1+
PD-L1+ Plac +P- – ITT population: 7% vs 2%
nabPx
nab-P nabPx
P nabPx
nab-P nabPx
nab-P
– PD-L1+ patients: 10% vs 1%
DOR, median 7.4 5.6 8.5 5.5
(95% CI), mo (6.9, 9.0) (5.5, 6.9) (7.3, 9.7) (3.7, 7.1)
No. of ongoing
78 (31%) 52 (25%) 39 (36%) 19 (24%)
responses, n (%)c

Schmid P, et al. N Engl J Med. 2018 Nov 29;379(22):2108-2121

 Primary PFS analysis: PD-L1+ population
100 Stratified HR = 0.62 Atezo + nab-P Plac + nab-P
(n = 185) (n = 184)
(95% CI: 0.49, 0.78)
Progression-free survival

PFS events, n 138 157

80 P < 0.0001 1-year PFS 29% 16%
(95% CI), % (22, 36) (11, 22)
60

40 As opposed to what is observed in melanoma and lung cancer,

there is NO tail of the PFS curve in TNBC

20
5.0 mo 7.5 mo
(3.8, 5.6) (6.7, 9.2)
0
0 3 6 9 12 15 18 21 24 27 30 33
Months
No. at risk:
Atezo + nab-P 185 146 104 75 38 19 10 6 2 1 NE NE
Plac + nab-P 184 127 62 44 22 11 5 5 1 NE NE NE

Data cutoff: 17 April 2018. Schmid P, et al. N Engl J Med. 2018 Nov 29;379(22):2108-2121
IMpassion 130: OS in the PDL1+ Subset @ 20m Follow up

△ mOS = 7.5m

ITT population:
18.7 vs 21.0m;
no impact in PDL1-

Emens et al, ESMO 2020

 KEYNOTE-355 Study Design (NCT02819518)
Key Eligibility Criteria
• Age ≥18 years
• Central determination of TNBC and
PD-L1 expression
Pembrolizumab a + Chemotherapyb
• Previously untreated locally
recurrent inoperable or metastatic
R Progressive
TNBC
disease d/cessation
• Completion of treatment with 2:1
curative intent ≥6 months prior to of study therapy
first disease recurrence
• ECOG performance status 0 or 1
Placebo c + Chemotherapyb
• Life expectancy ≥12 weeks from
randomization
• Adequate organ function
• No systemic steroids
• No active CNS metastases
• No active autoimmune disease Stratification Factors:
• Chemotherapy on study (taxane vs gemcitabine/carboplatin)
• PD-L1 tumor expression (CPS ≥1 vs CPS <1)
• Prior treatment with same class chemotherapy in the
neoadjuvant or adjuvant setting (yes vs no)

aPembrolizumab 200 mg intravenous (IV) every 3 weeks (Q3W) cNormal saline

bChemotherapy dosing regimens are as follows: dTreatment may be continued until confirmation of progressive disease
Nab-paclitaxel 100 mg/m 2 IV on days 1, 8, and 15 every 28 days CNS=central nervous system; ECOG=Eastern Cooperative Oncology Group;
Paclitaxel 90 mg/m 2 IV on days 1, 8, and 15 every 28 days PD-L1=programmed death ligand 1; R=randomized; TNBC=triple-negative breast cancer
Gemcitabine 1000 mg/m 2/carboplatin AUC 2 on days 1 and 8 every 21 days
 Progression-Free Survival: PD-L1 CPS ≥10
100 HR P-value
65.0% n/N Events
39.1% (95% CI) (one-sided)
90 46.9%
23.0% Pembro + Chemo 136/220 61.8% 0.65 0.0012a
80 (0.49-0.86)
Percentage of Patients
Placebo + Chemo 79/103 76.7%

70
60
9.7 months
50
5.6 months
40
30
20
10
0
0 3 6 9 12 15 18 21 24 27 30 33 36
Time, months
No. at risk
220 173 122 96 63 52 44 37 25 12 5 0 0
103 80 41 30 18 15 12 8 8 7 3 1 0
aPrespecified P value boundary of 0.00411 met.
Hazard ratio (CI) analyzed based on a Cox regression model with treatment as a covariate stratified by the randomization stratification factors. Data cutoff December 11, 2019.
 Progression-Free Survival: PD-L1 CPS ≥1
100 HR P-value
56.4% n/N Events
(95% CI) (one-sided)
90 46.6% 31.7%
19.4% Pembro + Chemo 288/425 67.8% 0.74 0.0014a
(0.61-0.90)
80 Placebo + Chemo 162/211 76.8%
Percentage of Patients

70
60
7.6 months
50 5.6 months
40
30
20
10
0
0 3 6 9 12 15 18 21 24 27 30 33 36
Time, months
No. at risk
425 315 202 143 94 72 60 51 32 16 6 0 0
211 158 81 51 28 20 17 11 10 8 3 1 0
aPrespecified P value boundary of 0.00111 not met.
Hazard ratio (CI) analyzed based on a Cox regression model with treatment as a covariate stratified by the randomization stratification factors. Data cutoff December 11, 2019.
 Progression-Free Survival: ITT
100 HR
55.4% n/N Events
(95% CI)
90 47.8% 29.8%
20.9% Pembro + Chemo 391/566 69.1% 0.82
80 (0.69-0.97)
Percentage of Patients
Placebo + Chemo 211/281 75.1%

70
60
7.5 months
50
5.6 months
40
30
20
10
0
0 3 6 9 12 15 18 21 24 27 30 33 36
Time, months
No. at risk
566 408 260 184 118 86 70 57 32 16 6 0 0
281 214 108 68 39 29 24 17 14 11 5 1 0
Hazard ratio (CI) analyzed based on a Cox regression model with treatment as a covariate stratified by the randomization stratification factors.
Statistical significance was not tested due to the prespecified hierarchical testing strategy. Data cutoff December 11, 2019.
 Treatment-Related AEs
Pembro + Placebo +
Chemo Chemo
100 All Treatment-Related (N = 562) (N = 281)
Any grade 96.3% 95.0% Grade
90
1-2 ≥3
Grade 3-5 68.1% 66.9%
80 Pembro + Chemo
Led to death 0.4%a 0.0%
70 Placebo + Chemo
Led to discontinuation 18.1% 11.0%
of any drug
Incidence, %

60

48.9
50 45.9
41.1 39.3 40.9
40 38.1
33.1 33.5
30 28.5 29.5
26.3
22.2 20.5
20 16.4

10

Treatment-Related AEs with Incidence ≥20% in Either Treatment Group

a1 patient from acute kidney injury and 1 patient from pneumonia. Data cutoff date: December 11, 2019.
 Immune-Mediated AEs
20
Pembro + Placebo +
18
Chemo Chemo
(N = 562) (N = 281)
Grade
16 15.5 Any grade 25.6% 6.0% 1-2 ≥3

14 Grade 3-5 5.2% 0.0% Pembro + Chemo

Led to death 0.0% 0.0% Placebo + Chemo

Incidence, %

12
Led to discontinuation 3.9% 1.1%
10 of any drug
8

6
4.8
4 3.2
2.5
1.8 0.4 1.8
2 1.1
0 0.4
0

Immune-Mediated AEs with Incidence ≥10 Patients in Either Treatment Groupa

aBased on a list of terms prespecified by the sponsor and included regardless of attribution to study treatment or immune relatedness by the investigator; related terms included.
Data cutoff date: December 11, 2019.
• Treatment choices in 1L PD-L1+ mTNBC
• Hypothesis on varying outcomes in 1L mTNBC trials (KN355 / IM130 / IM131)
• PD-L1 testing in 1L mTNBC (22C3 / SP142)

KEYNOTE-355 IMPASSION130 IMPASSION131

 Sacituzumab Govitecan (SG) Is a First-in-Class
Trop-2‒Directed ADC
• Trop-2 is expressed in all subtypes of breast
cancer and linked to poor prognosis1,2 Linker for SN-38 Humanized
• Hydrolyzable linker for anti‒Trop-2
• SG is distinct from other ADCs3-6 payload release antibody
• High drug-to-antibody • Directed toward
- Antibody highly specific for Trop-2
ratio (7.6:1)6 Trop-2, an
- High drug-to-antibody ratio (7.6:1) epithelial
- Internalization and enzymatic cleavage by antigen
tumor cell not required for the liberation of expressed on
many solid
SN-38 from the antibody
cancers
- Hydrolysis of the linker also releases the
SN-38 cytotoxic extracellularly in the tumor
microenvironment, providing a bystander effect
SN-38 payload
• Granted accelerated approval by the FDA for • SN-38 more
metastatic TNBC and fast-track designation in potent than
parent
metastatic urothelial cancer7 compound,
irinotecan

ADC, antibody−drug conjugate; TNBC, triple-negative breast cancer; Trop-2, trophoblast cell surface antigen 2.
1. Vidula N et al. J Clin Oncol. 2017;35:15(suppl):Abstract 1075. 2. Ambrogi et al. PLoS One. 2014;9(5):e96993. 3. Goldenberg DM et al. Expert Opin Biol Ther. 2020
Aug;20(8):871-885. 4. Nagayama A et al. Ther Adv Med Oncol. 2020;12:1758835920915980. 5. Cardillo TM et al. Bioconjugate Chem. 2015;26:919-931. 6. Goldenberg DM et al.
Oncotarget. 2015;6:22496-224512. 7. Press Release. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-sacituzumab-govitecan-hziy-
metastatic-triple-negative-breast-cancer. Accessed August 26, 2020.
 ASCENT: A Phase 3 Confirmatory Study of
Sacituzumab Govitecan in Refractory/Relapsed mTNBC
Metastatic TNBC Sacituzumab Govitecan (SG) Endpoints
(per ASCO/CAP) 10 mg/kg IV
days 1 & 8, every 21-day cycle Primary
Continue
≥2 chemotherapies for • PFS†
(n=267) treatment until
advanced disease R progression Secondary
[no upper limit; 1 of the required 1:1 or • PFS for the full
unacceptable
prior regimens could be from Treatment of Physician’s toxicity population‡
progression that occurred within Choice (TPC)* • OS, ORR,
a 12-month period after (n=262) DOR, TTR,
completion of (neo)adjuvant safety
therapy)]
N=529 Stratification factors Data cutoff: March 11, 2020
• Number of prior chemotherapies (2-3 vs >3)
NCT02574455 • Geographic region (North America vs Europe)
• Presence/absence of known brain metastases (yes/no)
ASCENT was halted early due to compelling evidence of efficacy per unanimous DSMC recommendation.
Here, we report the primary results from ASCENT, including PFS and OS.
*TPC: eribulin, vinorelbine, gemcitabine, or capecitabine. †PFS measured by an independent, centralized, and blinded group of radiology experts who assessed tumor response using
RECIST 1.1 criteria in patients without brain metastasis. ‡The full population includes all randomized patients (with and without brain metastases). Baseline brain MRI only required for
patients with known brain metastasis.
ASCO/CAP, American Society of Clinical Oncology/College of American Pathologists; DOR, duration of response; DSMC, Data Safety Monitoring Committee; IV, intravenous;
mTNBC, metastatic triple-negative breast cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; R, randomization; RECIST, Response
Evaluation Criteria in Solid Tumors; TTR, time to response.
National Institutes of Health. https://clinicaltrials.gov/ct2/show/NCT02574455.
 Disposition
Patients Screened
N=730

Patients Randomized
N=529

Safety All TPC* (eribulin, capecitabine, Safety

All SG
population† (n=267)
gemcitabine, or vinorelbine) population†
(n=258) (n=262) (n=224)

BMNeg population‡ BMNeg population‡

(Primary analysis) (Primary analysis)
Discontinuations (n=201)
Discontinuations (n=213) (n=235) (n=233) • n=166 Progressive disease
• n=199 Progressive disease • n=17 Consent withdrawal
• n=6 Adverse events • n=7 Adverse events
• n=4 Consent withdrawal • n=4 Physician decision
• n=3 Physician decision • n=4 Death
• n=1 Death§ Remain on treatment Remain on treatment • n=2 Treatment delay >3 wk
(n=0) • n=1 Unacceptable toxicity
(n=15)

*Patients in the TPC arm were randomized to: eribulin (n=139); vinorelbine (n=52); gemcitabine (n=38); capecitabine (n=33).
†All
patients who received ≥1 dose of study treatment. ‡Seven pts in the SG arm and 32 pts in the TPC arm were randomized but not treated in the brain metastases-negative population.
§This
was considered unlikely to be related to SG treatment. 76
BMNeg, brain metastases-negative; SG, sacituzumab govitecan; TPC, treatment of physician’s choice.
 Demographics and Patient Characteristics
SG (n=235) TPC (n=233) SG (n=235) TPC (n=233)
Female—no. (%) 233 (99) 233 (100) Previous anticancer regimens†
4 (2-17) 4 (2-14)
—median no. (range)
Median age—yr (range) 54 (29-82) 53 (27-81)
Race or ethnic group—no. (%) Most common previous chemotherapy—no. (%)
White 188 (80) 181 (78) Taxane‡ 235 (100) 233 (100)
Black 28 (12) 28 (12)
Anthracycline§ 191 (81) 193 (83)
Asian 9 (4) 9 (4)
Cyclophosphamide 192 (82) 192 (82)
Other or not specified 10 (4) 15 (6)
ECOG PS—no. (%) Carboplatin 147 (63) 160 (69)
0 108 (46) 98 (42)
Capecitabine 147 (63) 159 (68)
1 127 (54) 135 (58)
Previous PARP inhibitor—no. (%) 17 (7) 18 (8)
BRCA 1/2 mutational status—no. (%)
Positive 16 (7) 18 (8) Previous use of checkpoint inhibitors—no. (%) 67 (29) 60 (26)
Negative 133 (57) 125 (54)
Most common sites of diseaseΙΙ—no. (%)
Unknown 86 (37) 90 (39)
TNBC at initial diagnosis* Lung only 108 (46) 97 (42)

Yes 165 (70) 157 (67) Liver 98 (42) 101 (43)

No 70 (30) 76 (33) Bone 48 (20) 55 (24)
Brain metastases-negative population.
*Patients on study either had TNBC at initial diagnosis or had hormone receptor-positive disease that converted to hormone-negative at time of study entry. †Anticancer regimens refer to any treatment
regimen that was used to treat breast cancer in any setting ‡Includes: Paclitaxel, paclitaxel albumin, and docetaxel. §Includes: Doxorubicin, daunorubicin, epirubicin, and variations of those treatment
names. ΙΙBased on independent central review of target and non-target lesions.
BRCA, breast cancer gene; ECOG PS, Eastern Cooperative Oncology Group performance status; PARP, poly-ADP ribose polymerase; SG, sacituzumab govitecan; TNBC, triple-negative breast cancer;
TPC, treatment of physician’s choice.
77
 Progression-Free Survival (BICR Analysis)
BICR Analysis SG (n=235) TPC (n=233)
No. of events 166 150
Median PFS—mo (95% CI) 5.6 (4.3-6.3) 1.7 (1.5-2.6)
HR (95% CI), P-value 0.41 (0.32-0.52), P<0.0001

Primary endpoint (PFS) assessed by independent central review in the brain metastases-negative population, as pre-defined in the study protocol.
Secondary endpoint (PFS) assessed in the full population (brain metastases-positive and -negative) and PFS benefit was consistent (HR=0.43 [0.35-0.54], P<0.0001).
BICR, blind independent central review; PFS, progression-free survival; SG, sacituzumab govitecan; TPC, treatment of physician’s choice.
 Progression-Free Survival by Subgroup

Assessed by independent central review in brain metastases-negative population.

HR, hazard ratio; PFS, progression-free survival; SG, sacituzumab govitecan; TPC, treatment of physician’s choice.
 Overall Survival
SG (n=235) TPC (n=233)
No. of events 155 185
Median OS—mo (95% CI) 12.1 (10.7-14.0) 6.7 (5.8-7.7)
HR (95% CI), P-value 0.48 (0.38-0.59), P<0.0001

Assessed by independent central review in the brain metastases-negative population.

OS, overall survival; SG, sacituzumab govitecan; TPC, treatment of physician’s choice.
 Overall Response and Best Percent Change
From Baseline in Tumor Size
SG SG TPC
(n=235) (n=233)

ORR—no. (%) 82 (35) 11 (5)

***

P-value <0.0001

CR 10 (4) 2 (1)

PR 72 (31) 9 (4)

CBR—no. (%) 105 (45) 20 (9)

TPC
P-value <0.0001

Median DOR 6.3 3.6

****
—mo (95%CI) (5.5−9.0) (2.8−NE)

P-value 0.057

Assessed by independent central review in brain metastases-negative population.

*Denotes patients who had a 0% change from baseline in tumor size.
BICR, blind independent central review; CBR, clinical benefit rate (CR + PR + SD ≥6 mo); CR, complete response; DOR, duration of response; ORR, objective response rate;
PR, partial response; SG, sacituzumab govitecan; TPC, treatment of physician’s choice; TTR, time to response.
 TRAEs (All Grade, >20%; Grade 3/4, >5% of Patients)
SG (n=258) TPC (n=224)
TRAE* All grade % Grade 3, % Grade 4, % All grade, % Grade 3, % Grade 4, %
Neutropenia† 63 46 17 43 27 13
Anemia‡ 34 8 0 24 5 0
Hematologic
Leukopenia§ 16 10 1 11 5 1
Febrile neutropenia 6 5 1 2 2 <1
Diarrhea 59 10 0 12 <1 0
Gastrointestinal Nausea 57 2 <1 26 <1 0
Vomiting 29 1 <1 10 <1 0
Fatigue 45 3 0 30 5 0
Other
Alopecia 46 0 0 16 0 0
• Key grade ≥3 TRAEs (SG vs TPC): neutropenia (51% vs 33%), diarrhea (10% vs <1%), leukopenia (10% vs 5%), anemia (8% vs 5%), and
febrile neutropenia (6% vs 2%)
– G-CSF usage was 49% in the SG arm vs 23% in the TPC arm
– Dose reductions due to TRAEs were similar (22% SG vs 26% TPC)
• No severe cardiovascular toxicity, no grade >2 neuropathy or grade >3 interstitial lung disease with SG
• No treatment-related deaths with SG; 1 treatment-related death (neutropenic sepsis) with TPC
• AEs leading to treatment discontinuation were low for SG and TPC: 4.7% and 5.4%
• Patients received a median of 7 treatment cycles of SG, with a median treatment duration of 4.4 months (range, 0.03-22.9)
*Patients may report more than 1 event per preferred term. AEs were classified according to the MedDRA systems of preferred terms and system organ class and according to
severity by NCI CTCAE v4.03. †Combined preferred terms of ‘neutropenia’ and ‘decreased neutrophil count’. ‡Combined preferred terms of ‘anemia’ and ‘decreased hemoglobin’.
§Combined preferred terms of ‘leukopenia’ and ‘decreased white blood cell count’. 82
G-CSF, granulocyte-colony stimulating factor; SG, sacituzumab govitecan; TPC, treatment of physician’s choice; TRAE, treatment-related AE.
 Conclusions
• ASCENT is the first phase 3 study with Trop-2–directed ADC (sacituzumab govitecan [SG]) in pretreated
mTNBC to demonstrate a significant improvement over standard single-agent chemotherapy:
– Median PFS of 5.6 vs 1.7 months (HR 0.41, P<0.0001)
– Median OS of 12.1 vs 6.7 months (HR 0.48, P<0.0001)
– ORR of 35% vs 5%
– ORR, PFS, and OS benefit across all subgroups

• SG was well tolerated, with a manageable safety profile consistent with previous reports1
- AE leading to treatment discontinuation was low (4.7%)
- No severe cardiovascular toxicity, no grade >2 neuropathy or >3 interstitial lung disease
- No treatment-related deaths reported

• The randomized phase 3 study results confirm that SG should be considered as a new standard of care in
patients with pretreated mTNBC

• Ongoing studies are evaluating SG in earlier lines of therapy including neoadjuvant and adjuvant setting, in
combination with other targeted agents, and in patients with HR+ MBC (phase 3, TROPiCS-02)

ADC, antibody-drug conjugate; AE, adverse event; HR+, hormone receptor-positive; MBC, metastatic breast cancer; mTNBC, metastatic triple-negative breast cancer;
ORR, objective response rate; OS, overall survival; PFS, progression-free survival; SG, sacituzumab govitecan.
1. Bardia A et al. N Engl J Med. 2019;380:741-751.
 ASCENT Study Design Exploratory Analysis – TROP2 Expression

Trop-2 High Trop-2 Medium Trop-2 Low

H-score: 200-300 H-score: 100-200 H-score: <100
TPC TPC TPC
SG (n=85) SG (n=39) SG (n=27)
(n=72) (n=35) (n=32)
Median PFS –
6.9 2.5 5.6 2.2 2.7 1.6
mo.
95% CI (5.8-7.4) (1.5-2.9) (2.9-8.2) (1.4-4.3) (1.4-5.8) (1.4-2.7)
Median OS –
14.2 6.9 14.9 6.9 9.3 7.6
mo.
95% CI (11.3-17.5) (5.3-8.9) (6.9-NE) (4.6-10.1) (7.5-17.8) (5.0-9.6)

Efficacy summary by gBRCA status ORR – % (no.) 44% (37) 1% (1) 38% (15) 11% (4) 22% (6) 6% (2)
95% CI (33-55) (0-8) (23-55) (3-27) (9-42) (1-21)

Discussion Topic – Role of Sacituzumab in mTNBC

Sources: GS3-06, Sarah Hurvitz, Biomarker evaluation in the phase 3 ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative
breast cancer.
Triple negative breast cancer: Ladiratuzumab Vedotin

LIV1 is a transmembrane cell

adhesion molecule highly expressed
Protease-cleavable in metastatic breast cancer
linker Anti-LIV1 mAB

Mech. of Action:
MMAE 1. Binds to antigen
microtubule 2. Complex internalized and
disrupting trafficked to lysosome
agent 3. Release of MMAE payload
4. Microtubule disruption
5. Cell cycle arrest/disruption
 Triple negative breast cancer: Ladiratuzumab Vedotin

Confirmed ORR = 25% (15/60)

Modi S, et al. SABCS. 2017.

 Triple negative breast cancer: U3-1402

All 6.4 4.5

Dose: mg/kg mg/kg
N 42 15 15

ORR, % 43 60 40

DOR, % NR NR NR

DCR, % 91 100 87

mPFS, mo 8.3 6.4 4.6

Median 10.5 mo follow-up

Yonemori K, et al. Ann Oncol. 2019.

 Triple negative breast cancer: Combining ADC and IO
Ladiratuzumab Vedotin and Pembrolizumab:
ORR = 35%
>90%

• The efficacy evaluable population includes all treated subjects with at least one evaluable post-baseline assessment according to RECIST v1.1 or who had discontinued from the
study (N=69).
• Of the efficacy evaluable population, 5 subjects did not have evaluable response assessments before study discontinuation.

Han H, et al. SABCS. 2019.

 Research priorities

• Magnitude of clinical benefit scale for approval of agents with marginal

benefit
• More efforts to implement PROM
• Real life studies to evaluate effectiveness
• Integrating BIG DATA and moving from evidence based to real life evidence
based medicine
 Thank You

Giuseppe Curigliano MD, PhD

giuseppe.curigliano@ieo.it