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DESTINY-Breast03: Summary

  • In the updated OS analysis, T-DXd demonstrated:1,2
    • Clinically meaningful and statistically significant improvement in OS over T-DM1, as well as continued PFS benefit, in patients previously treated with trastuzumab and a taxane
      • T-DXd significantly reduced risk of death by 36% vs T-DM1 (HR, 0.64)
      • mPFS with T-DXd was significantly longer than with T-DM1 (28.8 months vs 6.8 months)
      • 78.5% of patients experienced a confirmed objective response; 1 in 5 (21.1%) experienced a CR
  • Consistent OS and PFS benefit was observed across key prespecified subgroups1,2
  • With a longer treatment duration, T-DXd continues to demonstrate a manageable and tolerable safety profile1,2
    • There were similar rates of grade ≥3 TEAEs with T-DXd and T-DM1
    • There were no grade 4 or 5 adjudicated drug-related ILD/pneumonitis events

  • Updated results demonstrate remarkable OS and PFS benefit with T-DXd, further supporting the use of T-DXd as the second-line standard of care in patients with HER2 positive metastatic BC1,2

  • T-DXd treatment demonstrated consistent efficacy benefit (PFS and ORR) over T-DM1 across patient subgroups3-6
    • Key patient subgroups were defined according to hormone receptor status, number of prior lines of therapy, history of brain metastases, geographic location, disease history (de novo or recurrent metastatic BC at diagnosis; visceral disease at baseline), setting of 1 prior line of systemic therapy (metastatic or [neo]adjuvant), and prior anti-HER2 therapy (number of prior lines; prior pertuzumab)
    • PFS and ORR were consistent between the overall population and key subgroups
    • Exposure-adjusted incidence rates of TEAEs were generally similar between subgroups and safety was consistent with the primary analysis
  • In patients with and without BMs at baseline, T-DXd treatment resulted in greater efficacy compared with T-DM13
  • T-DXd treatment is associated with substantial intracranial response and reduction in CNS disease3
  • In DESTINY-Breast03, the first randomized Phase III study of T-DXd in breast cancer, 309 participants (59% of the total) were from Asian countries (Republic of Korea, Japan, China, Taiwan, and Hong Kong)5
  • In the Asia subgroup analysis, T-DXd demonstrated:5
    • Clinically meaningful PFS benefit compared with T-DM1, which was consistent with that in the overall population
    • Safety profile was similar between the 2 arms, which was consistent with that seen in the overall population
  • Overall health status and QoL was maintained with T-DXd, based on mean change from baseline of EORTC QLQ-C30 GHS scale (primary PRO variable of interest) and other specified subscales of interest7
  • No new safety signals were observed for T-DXd in patients with HER2 positive metastatic BC in this safety update at September 7, 2021 DCO, and in-depth analysis demonstrated that:8
    • Most TEAEs were grade 1 or 2, and exposure-adjusted incidence rates of grade ≥3 TEAEs and serious TEAEs were lower with T-DXd than T-DM1
    • Risk of nausea, vomiting, fatigue, and alopecia was higher for T-DXd in the initial treatment cycles
    • Prevalence of nausea and vomiting was higher for T-DXd in the initial treatment cycles and was consistent over time for alopecia and fatigue
    • In the T-DXd arm, the increased risk and higher prevalence of these events that persisted throughout treatment duration necessitates ongoing supportive care
    • There was no additional grade 3 adjudicated ILD with T-DXd (overall rate = 0.8%), and no grade 4 or 5 events overall

Abbreviations

BC = breast cancer

;

BM = brain metastases

;

CNS = central nervous system

;

CR = complete response

;

DCO = data cut-off

;

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

;

GHS = global health status

;

HER2 = human epidermal growth factor receptor 2

;

HR = hazard ratio

;

ILD = interstitial lung disease

;

mPFS = median progression-free survival

;

ORR = objective response rate

;

OS = overall survival

;

PFS = progression-free survival

;

PRO = patient-reported outcome

;

QoL = quality of life

;

T-DM1 = trastuzumab emtansine

;

T-DXd = trastuzumab deruxtecan

;

TEAE = treatment-emergent adverse event

References

1. Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial [article]. The Lancet. 2022;401(10371):105-117.
2. Hurvitz SA, Hegg R, Chung WP, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: Updated results of the randomized, phase 3 study DESTINY-Breast03 [presentation and supplementary material]. Presented at: San Antonio Breast Cancer Symposium (SABCS) 2022 Annual Meeting; December 6-10, 2022.
3. Hurvitz SA, Kim SB, Chung WP, et al. Trastuzumab deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients with HER2+ metastatic breast cancer: subgroup analyses from the randomized phase 3 study DESTINY-Breast03 [presentation and abstract]. Presented at: San Antonio Breast Cancer Symposium (SABCS) 2021 Annual Meeting; December 7-10, 2021. Cancer Res. 2022;82(suppl 4). Abs GS3-01.
4. 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.
5. Im S-A, Xu B, Kim, S-B, et al. Trastuzumab deruxtecan vs T-DM1 in HER2+ mBC in Asian subgroup: Results of the randomized phase 3 study DESTINY-Breast03 [presentation]. Presented at: the Japanese Society of Medical Oncology Annual Meeting 2022; February 17-19, 2022. Presentation PS2-1.
6. Cortés J, Im SA, Iwata H, et al. Subgroup analysis by disease history and prior treatments of patients with HER2-positive metastatic breast cancer from DESTINY-Breast03, a randomized phase 3 study of trastuzumab deruxtecan vs trastuzumab emtansine [poster and abstract]. Poster presented at: European Society for Medical Oncology (ESMO) Virtual Congress 2022; September 9-13, 2022. Ann Oncol. 2022;33(suppl 7). Abs 236P.
7. 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.
8. Hamilton E, Petry V, Yeo W, et al. Trastuzumab deruxtecan vs trastuzumab emtansine in patients with HER2-positive unresectable and/or metastatic breast cancer: safety follow-up of the randomized, phase 3 study DESTINY-Breast03 [presentation and supplement]. Presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022. J Clin Oncol. 2022;40(suppl 16). Abs 1000.

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