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

Hurvitz, Sara A.; Hegg, Roberto; Chung, Weon Kuu; Im, Seock‐Ah; Jacot, William; Ganju, Vinod; Chiu, Joanne Wing Yan; Xu, Binghe; Hamilton, Erika; Madhusudan, Srinivasan; Iwata, Hiroji; Altıntaş, Sevilay; Henning, Jan-Willem; Curigliano, Giuseppe; Peréz-García, José Manuel; Kim, Sung‐Bae; Petry, Vanessa; Huang, Chiun‐Sheng; Li, Wei; Frenel, Jean‐Sébastien; Antolín, Silvia; Yeo, Winnie; Bianchini, Giampaolo; Loi, Sherene; Tsurutani, Junji; Egorov, Anton; Liu, Yali; Cathcart, Jillian; Ashfaque, Shahid; Cortés, Javier

doi:10.1016/s0140-6736(22)02420-5

Cited by 275 publications

(247 citation statements)

References 31 publications

(62 reference statements)

Supporting

Mentioning

161

Contrasting

Unclassified

Order By: Relevance

“…Recent data from the DESTINY-Breast03 trial revealed consistent efficacy benefit of T-DXd over trastuzumab emtansine across all subgroups analyzed, including patients with stable BMs. 22 , 23 Among 82 patients with stable BMs at baseline, median PFS was 15.0 months (95% CI, 12.5-22.2) in T-DXd arm vs 3.0 months (95% CI, 2.8-5.8) in trastuzumab emtansine arm (hazard ratio, 0.25; 95% CI, 0.13-0.45). However, the DESTINY-Breast03 trial precluded patients with clinically active BCBMs from being included.…”

Section: Discussionmentioning

confidence: 99%

Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: The DEBBRAH trial

et al. 2022

View full text Add to dashboard Cite

Background Trastuzumab deruxtecan (T-DXd) has shown durable antitumor activity in pretreated patients with HER2-positive advanced breast cancer (ABC), but its efficacy has not yet been evaluated in patients with active brain metastases (BMs). DEBBRAH aims to assess T-DXd in patients with HER2-positive or HER2-low ABC and central nervous system involvement. Methods This ongoing, five-cohort, phase II study (NCT04420598) enrolled patients with pretreated HER2-positive or HER2-low ABC with stable, untreated, or progressing BMs and/or leptomeningeal carcinomatosis. Here, we report findings from HER2-positive ABC patients with non-progressing BMs after local therapy (n=8; cohort 1), asymptomatic untreated BMs (n=4; cohort 2), or progressing BMs after local therapy (n=9; cohort 3). Patients received 5.4 mg/kg T-DXd intravenously once every 21 days. The primary endpoint was 16-week progression-free survival (PFS) for cohort 1 and intracranial overall response rate (ORR-IC) for cohorts 2 and 3. Results As of October 20, 2021, 21 patients received T-DXd. In cohort 1, 16-week PFS rate was 87.5% (95%CI, 47.3–99.7; P<.001). ORR-IC was 50.0% (95%CI, 6.7–93.2) in cohort 2 and 44.4% (95%CI, 13.7–78.8; P<.001) in cohort 3. Overall, the ORR-IC in patients with active BMs was 46.2% (95%CI, 19.2–74.9). Among patients with measurable intracranial or extracranial lesions at baseline, the ORR was 66.7% (12 out of 18 patients; 95%CI, 41.0–86.7), 80.0% (95%CI, 28.4–99.5) in cohort 1, 50.0% (95%CI, 6.7–93.2) in cohort 2, and 66.7% (95%CI, 29.9–92.5) in cohort 3. All responders had partial responses. The most common adverse events included fatigue (52.4%; 4.8% grade≥3), nausea (42.9%; 0% grade≥3), neutropenia (28.6%; 19% grade≥3), and constipation (28.6%; 0% grade≥3). Two (9.5%) patients suffered grade 1 interstitial lung disease/pneumonitis. Conclusions T-DXd showed intracranial activity with manageable toxicity and maintained quality of life in pretreated HER2-positive ABC patients with stable, untreated, or progressing BMs. Further studies are needed to validate these results in larger cohorts.

show abstract

Section: Discussionmentioning

confidence: 99%

Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: The DEBBRAH trial

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In addition, the updated OS data of DESTINY‑Breast 03 was presented at 2022 SABCS. Compared with T‐DM1, T‐DXd showed significantly improvement in OS (HR = 0.64, p = 0.0037) in patients with HER2‐positive MBC [10]. This updated results demonstrated remarkable survival benefit and tolerable safety for T‐DXd, supporting the T‐DXd as the second‐line standard treatment in patients with HER2‐positive MBC.…”

Section: Systemic Therapy For Breast Cancermentioning

confidence: 81%

Advances in medical treatment of breast cancer in 2022

Zhai

et al. 2023

Cancer Innovation

Self Cite

View full text Add to dashboard Cite

Breast cancer has replaced lung cancer as the most common malignancy worldwide. The 5-year survival rate of breast cancer has reached 90%. Systemic treatment of breast cancer has developed into a mature system including chemotherapy, targeted therapy, endocrine therapy and immunotherapy. This article summarizes the annual progress of breast cancer chemotherapy, targeted therapy, endocrine therapy and immunotherapy in 2022, providing valuable information for future research to better guide individualized treatment of breast cancer, thereby improving the prognosis and quality of life of breast cancer patients.

show abstract

“…Subsequent results from the landmark DESTINY-03 trial (phase III, randomized trial) in HER2+ MBC showed a dramatic improvement in PFS to 28.8 months from 6.8 months [hazard ratio (HR) 0.33, 95% confidence interval (CI): 0.26-0.43] with T-DXd compared to T-DM1 as a second-line therapy after treatment with trastuzumab and a taxane (13). A remarkable 21.1% of patients treated with T-DXd had a complete response vs. 9.5% in the T-DM1 group and OS was higher in the T-DXd arm (HR 0.64, P=0.0037) (13,14). Patient-reported outcomes revealed those treated with T-DXd had no significant change from baseline quality of life metrics, including emotional functioning and pain (15).…”

Section: T-dxdmentioning

confidence: 99%

Treatment of endocrine resistant metastatic breast cancer in the era of antibody drug conjugates

Heater¹,

Franco²,

Shah³

2023

Ann Transl Med

View full text Add to dashboard Cite

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

Cited by 275 publications

References 31 publications

Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: The DEBBRAH trial

Trastuzumab deruxtecan in patients with central nervous system involvement from HER2-positive breast cancer: The DEBBRAH trial

Advances in medical treatment of breast cancer in 2022

Treatment of endocrine resistant metastatic breast cancer in the era of antibody drug conjugates

Contact Info

Product

Resources

About