Safety

DESTINY-Breast08: Safety (Results from Part 1 Modules 4 [T-DXd + Anastrozole] and 5 [T-DXd + Fulvestrant] as of January 20, 2022 DCO)

Treatment Duration
Dose Modification
Safety Results

Treatment Duration

Medial Actual Treatment Duration¹

Median Actual Treatment Duration^a in Part 1/Modules 4 and 5¹

^aDose delays and interruptions were excluded in the analysis of actual treatment duration.

Dose Modification

Dose Modification¹

Dose Modifications in Part 1/Modules 4 and 5.¹

Treatment, n (%)	≥1 Dose Delay^a	≥1 Dose Reduction	≥1 Dose Interruption
Part 1/Module 4 (T-DXd + Anastrozole)
T-DXd	4 (66.7%) Reasons: AE (n=3)^b other (n=1)^c	0	0
Anastrozole	2 (33.3%) Reason: AE (n=2)^d	Dose modifications not allowed per protocol	1 (16.7%) Reason: AE^e
Part 1/Module 5 (T-DXd + Fulvestrant)
T-DXd	2 (33.3%) Reason: AE (n=1)^f other (n=2)^g	3 (50.0%) Reason: AE (n=3)^h	0
Fulvestrant	0	Dose modifications not allowed per protocol	1 (16.7%) Reason: otherⁱ

^aReasons for dose delays were not mutually exclusive; patients with multiple dose delays were counted only once per category; ^bAnemia (n=1), femoral neck fracture (n=1), and vomiting and pneumonitis (n=1); ^cMedication error (n=1); ^dVomiting and pneumonitis (n=1) and nasopharyngitis (n=1); ^eNasopharyngitis; ^fNausea (was updated from a dose interruption after the DCO); ^gPublic holiday (n=1) and assessment of possible disease progression (n=1; was updated from a dose interruption after the DCO); ^hNausea (n=2) and platelet count decreased (n=1); ⁱAssessment of possible disease progression.

Safety Results

Safety Results^1,2

The RDE was determined to be T-DXd 5.4 mg/kg IV Q3W + anastrozole 1 mg orally taken once a day for Part 1/Module 4 and T-DXd 5.4 mg/kg IV Q3W + fulvestrant 500 mg IM Q4W (loading dose: 500 mg on C1D15) for Part 1/Module 5. ^1,2
There were no DLTs reported in evaluable patients (both 6/6; 100%) and both combinations were generally well tolerated.
Two patients (33.3%) in Part 1/Module 4 and 3 patients (50.0%) in Part 1/Module 5 experienced grade ≥3 AEs. One patient (16.7%) in Part 1/Module 4 died 226 days after the first dose due to disease progression. No patients died in Part 1/Module 5.¹
No patients had ILD/pneumonitis in Part 1/Module 4. In Part 1/Module 5, 1 patient (16.7%) experienced drug-related ILD/pneumonitis outside the 28-day DLT cycle.¹

Safety Results with the RDE in Part 1/Modules 4 and 5.¹

n (%)	Module 4 T-DXd + Anastrozole n=6	Module 5 T-DXd + Fulvestrant n=6
Any AEs	6 (100)	6 (100)
Any grade ≥3 AE Hematologic Anemia Platelet count decreased Non-hematologic Femoral neck fracture Hypokalemia Nausea	2 (33.3) 2 (33.3) 0 1 (16.7) 1 (16.7) 0	3 (50.0) 1 (16.7) 1 (16.7) 0 1 (16.7) 1 (16.7)
Serious AEs	2 (33.3)^a	1 (16.7)^b
AEs leading to treatment discontinuation	0	1 (16.7)^c
AEs of special interest ILD/pneumonitis	0	1 (16.7)^d
Deaths	1 (16.7)^e	0

^aOne patient (16.7%) experienced 2 serious AEs, vomiting and anemia; neither were considered related to study drugs; the patient delayed T-DXd and anastrozole treatment due to the vomiting; the patient had recovered from the vomiting but the anemia had not resolved by the data cutoff. One (16.7%) patient experienced a serious AE of femoral neck fracture that was not considered related to study drugs; the patient delayed T-DXd treatment and the event was not resolved by the data cutoff; ^bOne patient (16.7%) experienced a serious AE of seizure that was not considered related to study drug; the seizure had resolved by the data cutoff; ^cPneumonitis; ^dOccurred outside of 28-day DLT period; ^eDue to disease progression, 226 days after first dose.

Abbreviations

AE = adverse event

;

DCO = data cut-off

;

DLT = dose limiting toxicity

;

ILD = interstitial lung disease

;

IM = intramuscular

;

IV = intravenous

;

Q3W = every 3 weeks

;

Q4W = every 4 weeks

;

RDE = recommended dose for expansion

;

T-DXd = trastuzumab deruxtecan

References

1. André F, Hamilton EP, Loi S, et al. Dose-finding and -expansion studies of trastuzumab deruxtecan in combination with other anticancer agents in patients with advanced/metastatic HER2+ (DESTINY-Breast07) and HER2-low (DESTINY-Breast08) breast cancer [poster, supplement, and abstract]. Poster presented at: American Society of Clinical Oncology (ASCO) 2022 Congress; June 3-5, 2022; Chicago, IL. J Clin Oncol. 2022;40(suppl 16). Abs 3025.
2. AstraZeneca. A phase 1b study of T-DXd combinations in HER2-low advanced or metastatic breast cancer (DB-08). ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT04556773

Document ID: 1592ad62-13a7-4b16-87ee-22c395bd8a67
Last updated: 09-December-2022

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