DCO November 20, 2023

DESTINY-Breast03: Efficacy Results (November 20, 2023 DCO Date)

Efficacy Summary
Objective Response Rate
Duration of Response
Progression-Free Survival
Overall Survival
Post-Trial Anticancer Systemic Treatment

Efficacy Summary

Efficacy Summary^1,2

Efficacy Summary by Investigator Assessment

	T-DXd n = 261	T-DM1 n = 263
OS,^a median (95% CI), months	52.6 (48.7-NE)	42.7 (35.4-NE)
HR (95% CI)	0.73 (0.56-0.94)
Patients with events (death), n (%)	110 (42.1)	126 (47.9)
Patients without events (censored), n (%) Alive Lost to follow-up	151 (57.9) 130 (49.8) 21 (8.0)	137 (52.1) 112 (42.6) 25 (9.5)
OS rate^b (95% CI), % 24 months 36 months 48 months	77.5 (71.8-82.2) 67.6 (61.3-73.0) 56.9 (50.2-63.1)	70.1 (64.0-75.4) 55.7 (49.2-61.7) 48.3 (41.7-54.5)
PFS,^a^,^c median (95% CI), months	29.0 (23.7-40.0)	7.2 (6.8-8.3)
HR (95% CI)	0.30 (0.24-0.38)
Patients with events, n (%) Progressive disease Death	129 (49.4) 120 (46.0) 9 (3.4)	197 (74.9) 189 (71.9) 8 (3.0)
Patients without events (censored), n (%)	132 (50.6)	66 (25.1)
PFS rate^b (95% CI), % 24 months 36 months 48 months	55.8 (49.1-62.0) 45.7 (38.9-52.2) 41.5 (34.6-48.3)	20.6 (15.4-26.4) 12.4 (8.1-17.7) 9.9 (5.9-15.1)
Confirmed ORR,^c n (%) (95% CI)^d CR, n (%) PR, n (%) SD, n (%) PD, n (%) NE, n (%)	206 (78.9) (73.5-83.7) 33 (12.6) 173 (66.3) 48 (18.4) 2 (0.8) 5 (1.9)	97 (36.9) (31.0-43.0) 11 (4.2) 86 (32.7) 119 (45.2) 34 (12.9) 13 (4.9)
DOR,^c^a median (95% CI), months DoR rate at 36 months (95%), %	30.5 (23.0-NE) 48.9 (41.3-56.1)	17.0 (14.1-23.7) 28.7 (18.9-39.2)
PFS2,^c^a^e median (95% CI), months	45.2 (39.3-NE)	23.1 (17.8-29.7)
HR (95% CI)	0.53 (0.41-0.68)

^aThe median is from Kaplan-Meier analysis. The CI for the median was computed using the Brookmeyer-Crowley method; ^bEstimate and CI for OS and PFS rates at the specified time point were from Kaplan-Meier analysis; ^cBy investigator assessment; ^dBased on the Clopper-Pearson method for single proportion and for the difference of two proportions with continuity correction; ^ePFS2 is defined as the PFS from time of randomization to progression on the next line of therapy or death.

Objective Response Rate

Objective Response Rate^1,2

Objective Response Rate by Investigator Assessment

T-DXd

n = 261

T-DM1

n = 263

cORR, n (%)

(95% CI)^a

CR, n (%)
PR, n (%)
SD, n (%)
PD, n (%)
NE, n (%)

206 (78.9)

(73.5-83.7)

33 (12.6)

173 (66.3)

48 (18.4)

2 (0.8)

5 (1.9)

97 (36.9)

(31.0-43.0)

11 (4.2)

86 (32.7)

119 (45.2)

34 (12.9)

13 (4.9)

DoR,^b median (95% CI), months

DoR rate at 36 months (95% CI), %

30.5 (23.0-NE)

48.9 (41.3-56.1)

17.0 (14.1-23.7)

28.7 (18.9-39.2)

^aBased on the Clopper-Pearson method for single proportion and for the difference of 2 proportions with continuity correction; ^bThe median is from Kaplan-Meier analysis. The CI for the median was computed using the Brookmeyer-Crowley method.

Duration of Response

Duration of Response^1,2

Duration of Response by Investigator Assessment^1,2^,a

<p>Duration of Response by Investigator Assessment<span class="tooltip"><span class="tooltip-text"><sup>1,2</sup></span><span class="tooltip-content" style="display: none;"><span>1. Cortés J, Hurvitz SA, Im S-A, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from the randomized, phase 3 DESTINY-Breast03 trial. <em>Nat Med</em>. 2024.</span><span>2. Hamilton E, Hurvitz SA, Im S-A, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated survival results from the randomized, phase<span> 3, DESTINY-Breast03 trial. Presented at: American Society for Clinical Oncology; May 31-June 4, 2024. Poster 1025</span></span></span></span><sup>,a</sup></p>

^aThe DoR rate at 36 months was 48.9% (95% CI, 41.3-56.1%) with T-DXd and 28.7% (95% CI, 18.9-39.2%) with T-DM1

Progression-Free Survival

Progression-Free Survival^1-3

Overall Survival

Overall Survival^1,2

Crosses indicate where data were censored, number of patients censored are not stated.

Sensitivity Analysis for OS^1,2^,a

<p>Sensitivity Analysis for OS<span class="tooltip"><span class="tooltip-text"><sup>1,2</sup></span><span class="tooltip-content" style="display: none;"><span>1. Cortés J, Hurvitz SA, Im S-A, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from the randomized, phase 3 DESTINY-Breast03 trial. <em>Nat Med</em>. 2024.</span><span>2. Hamilton E, Hurvitz SA, Im S-A, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated survival results from the randomized, phase<span> 3, DESTINY-Breast03 trial. Presented at: American Society for Clinical Oncology; May 31-June 4, 2024. Poster 1025</span></span></span></span><sup>,a</sup></p>

^aRPSFTM adjusted Kaplan-Meier curve of OS for the T DM1 group plotted with the unadjusted OS curves for the T-DXd group and T-DM1 group

Post-Trial Anticancer Systemic Treatment

Post-Trial Anticancer Systemic Treatment^1,2

Post-Trial Anticancer Systemic Treatment

	T-DXd n = 261	T-DM1 n = 263
Patients who discontinued treatment^a, n (%)	207 (80.5)	251 (96.2)
Patients assigned to undergo surgery^b	6 (2.9)	15 (6.0)
Patients assigned to receive radiation treatment^b	26 (12.6)	43 (17.1)
Patients assigned to received post-trial anticancer systemic treatment^b	144 (69.6)	198 (78.9)
Type of post-trial anticancer treatment^c, n (%)
Trastuzumab	57 (39.6)	103 (52.0)
T‑DXd	12 (8.3)	64 (32.3)
T-DM1	75 (52.1)	26 (13.1)
Pertuzumab	17 (11.8)	31 (15.7)
Taxane	22 (15.3)	38 (19.2)
Taxane and trastuzumab	12 (8.3)	33 (16.7)
Other HER2-directed therapy	57 (39.6)	102 (51.5)
HER2-directed TKI	52 (36.1)	95 (48.0)
Other HER2-directed antibody or ADC	13 (9.0)	23 (11.6)
Hormone therapy	29 (20.1)	41 (20.7)
Other systemic therapy	100 (69.4)	158 (79.8)

^aThe denominator for calculating the percentage was the number of patients who received at least 1 dose of study treatment (safety analysis set) in the T-DXd or T-DM1 group ^bThe denominator for calculating the percentage was the number of patients who discontinued study treatment inthe T-DXd or T-DM1 group; ^cThe denominator for calculating the percentage was the number of patients who were assigned to any anticancer systemic treatment in the T-DXd or T-DM1 group. Patients could have received more than one type of therapy.

Abbreviations

ADC = antibody-drug conjugate

;

CI = confidence interval

;

cORR = confirmed objective response rate

;

CR = complete response

;

DCO = data cutoff

;

DoR = duration of response

;

HER2 = human epidermal growth factor receptor 2

;

HR = hazard ratio

;

NE = not evaluable

;

ORR = objective response rate

;

OS = overall survival

;

PD = progressive disease

;

PFS = progression free survival

;

PFS2 = time to second progression or death

;

PR = partial response

;

RPSFTM = rank preserving structural failure time model

;

SD = stable disease

;

T-DM1 = trastuzumab emtansine

;

T-DXd = trastuzumab deruxtecan

;

TKI = tyrosine kinase inhibitor

References

1. Cortés J, Hurvitz SA, Im S-A, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from the randomized, phase 3 DESTINY-Breast03 trial. Nat Med. 2024.

2. Hamilton E, Hurvitz SA, Im S-A, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated survival results from the randomized, phase 3, DESTINY-Breast03 trial. Presented at: American Society for Clinical Oncology; May 31-June 4, 2024. Poster 1025

3. Hamilton E, Hurvitz SA, Im S-A, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated survival results from the randomized, phase 3, DESTINY-Breast03 trial. Presented at: American Society for Clinical Oncology; May 31- June 4, 2024. Poster 1025. [Supplement].

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Document ID: 8db67364-6c52-4ea0-b987-9d4900884ec2
Last updated: 27-June-2024

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