HEOR Subgroup Analysis

DESTINY-Breast03 HEOR Analyses: Results (May 21, 2021 DCO Date)

Rationale
HEOR Endpoints
HEOR Results

Rationale

Rationale for HEOR Analyses^1,2

PROs and quality of life should be considered alongside efficacy and safety to better understand treatment impact and minimize patient burden during treatment selection¹
Hospital admission is a clinically important event, and these data can yield insights into prevention strategies for minimizing disease burden on individuals and reducing costs for health services²
In addition to adverse event reporting (including hospitalizations) and clinical assessments made while on treatment to monitor patients’ health, this study captured the patient’s assessment of how their disease and treatment affect other aspects of their well-being and daily functioning over time²

HEOR Endpoints

HEOR Endpoints and Analyses²

HEOR Endpoints and Analyses.²

<p>HEOR Endpoints and Analyses.<span class="tooltip"><span class="tooltip-text"><sup>2</sup></span><span class="tooltip-content" style="display: none;"><span>2. <span style="background-color: rgb(252, 252, 252);">Curigliano G, Dunton K, Rosenlund M, et al. Patient-reported outcomes from DESTINY-Breast03, a randomized phase 3 study of trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer [presentation and abstract]. Presented at: European Society for Medical Oncology (ESMO) Breast Cancer 2022; May 3-5, 2022. </span><em style="background-color: rgb(252, 252, 252);">Ann Oncol</em><span style="background-color: rgb(252, 252, 252);">. 2022;33(suppl 3). Abs 1630.</span></span></span></span></p>

^aPrimary PRO variable of interest; ^bClinically meaningful deterioration defined as a change of 10 points or more in the GHS and subscale scores; ^cNot all variables measured were assessed for TDD; ^d1 cycle=21 days; T-DXd or T-DM1 administered on day 1 of each cycle; questionnaires completed before treatment on day 1 of cycles indicated.

HEOR Results

HEOR Results²

EORTC QLQ-C30 GHS Over Time^2-4

As of May 21, 2021, patients still receiving study drug included: T-DXd, 132 (51.4%) and T-DM1, 47 (18.0%)⁴
The median (range) treatment duration was 14.3 (0.7-29.8) months in the T-DXd arm and 6.9 (0.7-25.1) months in T-DM1 arm.³
Global health was maintained in patients treated with T-DXd while on treatment (until n <20 when results are no longer informative)²

EORTC QLQ-C30 GHS Over Time.²

<p>EORTC QLQ-C30 GHS Over Time.<span class="tooltip"><span class="tooltip-text"><sup>2</sup></span><span class="tooltip-content" style="display: none;"><span>2. <span style="background-color: rgb(252, 252, 252);">Curigliano G, Dunton K, Rosenlund M, et al. Patient-reported outcomes from DESTINY-Breast03, a randomized phase 3 study of trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer [presentation and abstract]. Presented at: European Society for Medical Oncology (ESMO) Breast Cancer 2022; May 3-5, 2022. </span><em style="background-color: rgb(252, 252, 252);">Ann Oncol</em><span style="background-color: rgb(252, 252, 252);">. 2022;33(suppl 3). Abs 1630.</span></span></span></span></p>

Note: Scores range from 0 to 100; a linear transformation was applied to the raw GHS score, thus a higher score represents lower ("worse") GHS/overall QoL.

Time to Definitive Deterioration²

Forest Plot²

TDD in PRO measures of interest.²

<p>TDD in PRO measures of interest.<span class="tooltip"><span class="tooltip-text"><sup>2</sup></span><span class="tooltip-content" style="display: none;"><span>2. <span style="background-color: rgb(252, 252, 252);">Curigliano G, Dunton K, Rosenlund M, et al. Patient-reported outcomes from DESTINY-Breast03, a randomized phase 3 study of trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer [presentation and abstract]. Presented at: European Society for Medical Oncology (ESMO) Breast Cancer 2022; May 3-5, 2022. </span><em style="background-color: rgb(252, 252, 252);">Ann Oncol</em><span style="background-color: rgb(252, 252, 252);">. 2022;33(suppl 3). Abs 1630.</span></span></span></span></p>

Note: P values are not adjusted for multiple testing. TDD is defined as a >10-point CFB.

^aPrimary PRO variable of interest; ^bSecondary PRO variable of interest.

Kaplan-Meier Analysis²

Patients treated with T-DXd experienced numerically longer median TDD of EORTC QLQ-C30 GHS (9.7 months with T-DXd and 8.3 months with T-DM1)²
Prolonged TDD was particularly pronounced with T-DXd vs T-DM1 for emotional functioning and pain symptoms scales²
TDD of the EQ-5D-5L VAS was prolonged in patients receiving T-DXd vs T-DM1²

Hospitalization-Related Endpoints²

Median time to hospitalization was more than 3 times longer in the T-DXd arm vs T-DM1 arm²
Other hospitalization outcomes were similar between treatment arms²

Hospitalization-Related Endpoints.

Parameter	T-DXd n=261	T-DM1 n=263
Subjects with hospitalization, n (%)	18 (6.9)	19 (7.2)
Median (range) time to first hospitalization^a, days	219.5 (0-723)	60.0 (0-399)
Median (range) length of hospital stay, days	10.5 (1-181)	9.0 (2-25)
Died, n (%)	2 (0.8)	1 (0.4)
Discharged home, n (%)	15 (5.7)	16 (6.1)
Discharged to home health care, n (%)	1 (0.4)	1 (0.4)

^aTime to first hospitalization is defined as the time from the date of randomization to the date of the first hospitalization during the study treatment (from date of first dose to 47 days after last dose). Time for subjects whose first hospitalization date was prior to treatment start date was calculated as 0..

Abbreviations

CFB = change from baseline

;

DCO = data cut-off

;

EORTC QLQ-BR45 = European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer C45

;

EORTC-QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30

;

EOT = end of treatment

;

EQ-5D-5L = EuroQol 5-dimension, 5-level questionnaire

;

GHS = global health status

;

HEOR = health economic outcomes research

;

HR = hazard ratio

;

HRQoL = health-related quality of life

;

NE = not evaluable

;

PRO = patient reported outcomes

;

QoL = quality of life

;

SD = stable disease

;

TDD = time to definitive deterioration

;

T-DM1 = trastuzumab emtansine

;

T-DXd = trastuzumab deruxtecan

;

VAS = visual analog scale

References

1. Cardoso F, Costa A, Senkus E, et al. 3rd ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3). Ann Oncol. 2017;28(1):16-33.

2. Curigliano G, Dunton K, Rosenlund M, et al. Patient-reported outcomes from DESTINY-Breast03, a randomized phase 3 study of trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer [presentation and abstract]. Presented at: European Society for Medical Oncology (ESMO) Breast Cancer 2022; May 3-5, 2022. Ann Oncol. 2022;33(suppl 3). Abs 1630.

3. Cortés J, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med. 2022;386:1143-1154.

4. Cortés J, Kim SB, Chung WP, et al. Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer (mBC): results of the randomized, phase 3 study DESTINY-Breast03 [presentation and abstract]. Presented at: European Society for Medical Oncology; September 16-21, 2021. Ann Oncol. 2021;32(suppl 5). Abstract LBA1.

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